Javier Angeles-martínez - Academia.edu (original) (raw)

Papers by Javier Angeles-martínez

Copyright © 2015 Irma Eloisa Monroy-Muñoz et al. This is an open access article distributed unde... more Copyright © 2015 Irma Eloisa Monroy-Muñoz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. The relevance of TBX20 gene in heart development has been demonstrated in many animal models, but there are few works that try to elucidate the effect of TBX20 mutations in human congenital heart diseases. In these studies, all missense mutations associated with atrial septal defect (ASD) were found in the DNA-binding T-box domain, none in the transcriptional activator domain. Methods. We search for TBX20 mutations in a group of patients with ASD or ventricular septal defect (VSD) using the High Resolution Melting (HRM) method and DNA sequencing. Results. We report three missense mutations (Y309D, T370O, and M395R) within the transcriptional activator domain of human TBX20 that were associated with ASD. Conclus...

Aim The role of interleukin 17A (IL-17A) in the inflammatory process has caused interest in the p... more Aim The role of interleukin 17A (IL-17A) in the inflammatory process has caused interest in the potential significance of IL-17A as a biomarker for coronary artery disease (CAD). The aim of the present study was to evaluate the role of IL-17A gene polymorphisms as susceptibility markers for CAD in the Mexican population. Methods Four IL-17A gene polymorphisms (rs8193036, rs3819024, rs2275913 and rs8193037) were genotyped by 5 ’ exonuclease TaqMan assays in a group of 900 patients with prema-ture CAD and 667 healthy controls (with negative calcium score by computed tomography), seeking associations with CAD and other metabolic and cardiovascular risk factors using lo-gistic regression analyses. Results No single IL-17A polymorphism was associated with premature CAD, however two haplo-types (CAGG and TAGA) were significantly associated with increased risk of premature

Cytokine, 2018

Interleukin 10 (IL-10) is an anti-inflammatory cytokine with a protective role in the formation a... more Interleukin 10 (IL-10) is an anti-inflammatory cytokine with a protective role in the formation and the development of the atherosclerotic plaque. The aim of the present study was to establish if IL-10 gene polymorphisms are associated with the development of premature coronary artery disease (pCAD) and cardiovascular risk factors in Mexican individuals. Three IL-10 gene polymorphisms [-592C/A (rs1800872), -819C/T (rs1800871), and -1082 A/G (rs1800896)] and IL-10 plasma levels were analyzed in 2266 individuals (1160 pCAD patients and 1106 healthy controls). Under recessive and co-dominant2 models, the -1082 A/G (rs1800896) G allele was associated with decreased risk of developing pCAD (OR = 0.572, P = 0.022 and OR = 0.567, P = 0.023). In pCAD patients, the polymorphisms were associated with hyperinsulinemia, small and dense LDLs, hypertension, and diabetes mellitus. In the control group, the polymorphisms were associated with hypertension, hyperuricemia, and small and dense LDLs. pC...

Cytokine, 2017

Interleukin IL-15 (IL-15) has been implicated in the development of coronary artery disease (CAD)... more Interleukin IL-15 (IL-15) has been implicated in the development of coronary artery disease (CAD). The aim of the present study was to evaluate the role of IL-15 gene polymorphisms as susceptibility markers for development of subclinical atherosclerosis (SA) and cardiovascular risk factors in Mexican population. Four IL-15 gene polymorphisms (rs4956403, rs3806798, rs1057972 and rs10833) were analyzed in a group of 397 individuals with SA and 1120 controls. Under different inheritance models adjusted by traditional risk factors, the rs10833 T allele was associated with increased risk of developing SA [OR = 1.42, P codom1 = 0.046; OR = 1.48, P dom = 0.021; OR = 1.43, P add = 0.014]. Under a dominant model, the rs1057972 polymorphism was associated with central obesity (P = 0.045) and fatty liver (P = 0.021), while the rs10833 polymorphism was associated with metabolic syndrome (P = 0.007) in individuals with SA. The TAC haplotype was significantly associated with a decreased risk of SA. Individuals with rs10833CC genotype exhibited higher levels of IL-15 than individuals with CT + TT genotypes. The results suggest that IL-15 polymorphisms are involved in the risk of developing SA and are associated with metabolic syndrome, central obesity and fatty liver in our study population. The rs10833 polymorphism could be involved in regulating IL-15 production in SA.

Mediators of Inflammation, 2017

Interleukin 35 (IL-35) is a heterodimeric cytokine involved in the development of atherosclerosis... more Interleukin 35 (IL-35) is a heterodimeric cytokine involved in the development of atherosclerosis. The aim of the present study was to establish if the polymorphisms ofIL-12AandEBI3genes that encode the IL-35 subunits are associated with the development of premature coronary artery disease (CAD) in Mexican individuals. TheIL-12AandEBI3polymorphisms were determined in 1162 patients with premature CAD and 873 controls. Under different models, theEBI3rs428253 (OR = 0.831,Padd= 0.036; OR = 0.614,Prec= 0.033; OR = 0.591,Pcod2= 0.027) andIL-12Ars2243115 (OR = 0.674,Padd= 0.010; OR = 0.676,Pdom= 0.014; OR = 0.698,Phet= 0.027; OR = 0.694,Pcod1= 0.024) polymorphisms were associated with decreased risk of developing premature CAD. Some polymorphisms were associated with clinical and metabolic parameters. Significant different levels of IL-35 were observed inEBI3rs4740 and rs4905 genotypes only in the group of healthy controls. In summary, our study suggests that theEBI3andIL-12Apolymorphisms ...

Experimental and Molecular Pathology, 2017

The receptor-interacting protein 2 (Rip2) is a serine/threonine kinase involved in multiple nucle... more The receptor-interacting protein 2 (Rip2) is a serine/threonine kinase involved in multiple nuclear factor-κB (NFκB) activation pathways and is a key regulator of cellular lipid metabolism and cardiovascular disease. The aim of the present study was to evaluate the role of RIP2 gene polymorphisms as susceptibility markers for subclinical atherosclerosis (SA). Using an informatics analysis, four RIP2 gene polymorphisms with predicted functional effects (rs2293808, rs43133, rs431264, and rs16900627) were selected. The polymorphisms were genotyped in 405 individuals with SA (calcium score N 0 assessed by computed tomography) and 1099 controls (calcium score = 0). Clinical, anthropometric, tomographic and biochemical traits were measured. The association between the RIP2 polymorphisms and SA was evaluated using logistic regression analyses. Pair wise linkage disequilibrium (LD, D′) estimations between polymorphisms and haplotype reconstruction were performed with Haploview version 4:1. Under different models adjusted by age, gender, body mass index, hypertension, diabetes mellitus, smoking habit, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels, rs43133 (OR = 1.43, 95% CI: 1.05-1.94, P = 0.022), and rs16900627 (OR = 1.59, 95% CI: 1.00-2.54, P dom = 0.048 and OR = 1.60, 95% CI: 1.05-2.54, P add = 0.028) were associated with increased risk of developing SA. Moreover, rs2293808, and rs431264 were associated with clinical or metabolic parameters in SA individuals and in healthy controls. The four polymorphisms were in high linkage disequilibrium and the GAAG haplotype was associated with increased risk of developing SA (OR = 1.47, P = 0.027). This study shows for the first time, that RIP2 polymorphisms are associated with increased risk of SA and with some clinical and metabolic parameters.

Global Heart, 2016

3%). Majority of the PCI (60-80%) were elective cases. There is an increasing trend of number of ... more 3%). Majority of the PCI (60-80%) were elective cases. There is an increasing trend of number of procedures in January 2014 (n¼483) and June 2014 (n¼561). Programme costs varied considerably across all facilities, and consumables alone contribute an average 69.41%, with median RM 8,437.82 (RM 7,566.98-13,070.58). The estimated costs of PCI in this study, median RM 13,876.67 (RM11,518.00-15,025.04). Significantly lower costing is found in hospital which performed more numbers of elective cases in daycare. The overall inhospital all-cause mortality (including emergency cases) was 3.2% (n¼57) from January until June 2014. The discrepancy of mortality rate was mainly contributed by the emergency PCI cases. Conclusion: The six selected public, institution and teaching hospitals showed an increased number of PCI procedures performed in midyear as compared to earlier part of the year. The overall in-hospital all-cause mortality remained acceptably low but the scarcity of operational cost is non-related factor.

BioMed Research International, 2015

Background. The relevance ofTBX20gene in heart development has been demonstrated in many animal m... more Background. The relevance ofTBX20gene in heart development has been demonstrated in many animal models, but there are few works that try to elucidate the effect ofTBX20mutations in human congenital heart diseases. In these studies, all missense mutations associated with atrial septal defect (ASD) were found in the DNA-binding T-box domain, none in the transcriptional activator domain.Methods. We search forTBX20mutations in a group of patients with ASD or ventricular septal defect (VSD) using the High Resolution Melting (HRM) method and DNA sequencing.Results. We report three missense mutations (Y309D, T370O, and M395R) within the transcriptional activator domain of human TBX20 that were associated with ASD.Conclusions. This is the first association of TBX20 transcriptional activator domain missense mutations with ASD. These findings could have implications for diagnosis, genetic screening, and patient follow-up.

Experimental and Molecular Pathology, 2014

The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of d... more The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing in-stent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5' exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR=1.31, 95% CI: 1.04-1.66, P=0.018) and decreased frequencies of GAGATG (OR=0.47, 95% CI: 0.25-0.88, P=0.011) and AGAGCA (OR=0.15, 95% CI: 0.02-0.65, P=0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.

Nephrology, 2010

The TGF-β gene participates in the development of chronic kidney disease. We investigated whether... more The TGF-β gene participates in the development of chronic kidney disease. We investigated whether the 869 T > C, 915 G > C and -800 G > A polymorphisms of TGF-β1 are associated with diabetic nephropathy (DN). Polymorphisms were genotyped in 439 type 2 diabetes mellitus patients, 233 with diabetic nephropathy (DN+) and 206 without (DN-). The sample was characterized for relevant clinical and biochemical parameters. The 869 T > C (P = 0.016; odds ratio (OR) = 1.818, 95% confidence interval (CI) = 1.128-2.930) and the 915 G > C polymorphisms (P = 0.008, OR = 4.073, 95% CI = 1.355-12.249) were associated with diabetic nephropathy. The 869 T > C variant was associated with total cholesterol levels: CC + CT genotypes had a mean cholesterol concentration of 5.62 ± 1.40 mmol/L vs a mean concentration of 5.15 ± 1.40 mmol/L for the TT genotype (P = 0.011). Triglycerides were also higher in CC + CT genotypes (2.49 ± 1.56 mmol/L) in comparison with TT homozygotes (2.1 ± 1.22 mmol/L, P = 0.042). Multivariate logistic regression showed that the polymorphisms 869 T…

Journal of Translational Medicine, 2013

Background The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition ... more Background The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence. Methods We carried out a case–control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts. Results We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcor...

Diabetes/Metabolism Research and Reviews, 2010

Background Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors.... more Background Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors. Metabolic syndrome (MS) increases the risk of cardiovascular disease and diabetes. We analysed 14 cases of polymorphisms located in 10 candidate loci, in a sample of patients with T2D and controls from Mexico City. Methods We analysed the association of 14 polymorphisms located within 10 genes (TCF7L2, ENPP1, ADRB3, KCNJ11, LEPR, PPARγ , FTO, CDKAL1, SIRT1 and HHEX) with T2D and MS. The analysis included 519 subjects with T2D defined according to the ADA criteria, 389 with MS defined according to the AHA/NHLBI criteria and 547 controls. Association was tested with the program ADMIXMAP including individual ancestry, age, sex, education and in some cases body mass index (BMI), in a logistic regression model. Results The two markers located within the TCF7L2 gene showed strong associations with T2D (rs7903146, T allele, odd ratio (OR) = 1.76, p = 0.001 and rs12255372, T allele, OR = 1.78, p = 0.002), but did not show significant association with MS. The non-synonymous rs4994 polymorphism of the ADRB3 gene was associated with T2D (Trp allele, OR = 0.62, p = 0.001) and MS (Trp allele, OR = 0.74, p = 0.018). Nominally significant associations were also observed between T2D and the SIRT1 rs3758391 SNP and MS and the HHEX rs5015480 polymorphism. Conclusions Variants located within the gene TCF7L2 are strongly associated with T2D but not with MS, providing support to previous evidence indicating that polymorphisms at the TCF7L2 gene increase T2D risk. In contrast, the non-synonymous ADRB3 rs4994 polymorphism is associated with T2D and MS.

Immunologic Research, 2017

The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-I... more The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR'3 G37562-C (rs10754558)] were genotyped by 5' exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08-2.86, P Res = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07-2.85, P Res = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR'3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22-0.92, P Co-dom = 0.006; OR = 0.61, 95%CI 0.44-0.84, P Dom = 0.002; OR = 0.67, 95%CI 0.48-0.94, P Over-dom = 0.02; and OR = 0.65, 95%CI 0.50-0.94, P Add = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR'3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.

Written Communication, 2000

The issues of authentic context and authoritative ethos are explored through a study of a graduat... more The issues of authentic context and authoritative ethos are explored through a study of a graduate student learning to write for mathematics within the context of an English for academic purposes (EAP) course. The student faced conflicts about audience, purpose, and content knowledge as she was required to write math texts within what she perceived was an inauthentic context, an English as a second language (ESL) course. She questioned the purpose of the writing tasks as well as why an ESL instructor was teaching her to write for math, and she addressed the conflicts by writing for the instructor's discourse community and expectations, rather than her own, to earn a grade for the course. The text the student created was thus inauthentic within her own discourse community and lacked her voice of authority. These findings question the validity of EAP courses and raise several issues, especially in terms of the transferability of skills from EAP to content courses.

PLOS ONE, 2017

Background Acute respiratory infections are the leading cause of morbidity and mortality worldwid... more Background Acute respiratory infections are the leading cause of morbidity and mortality worldwide. Although a viral aetiological agent is estimated to be involved in up to 80% of cases, the majority of these agents have never been specifically identified. Since 2009, diagnostic and surveillance efforts for influenza virus have been applied worldwide. However, insufficient epidemiological information is available for the many other respiratory viruses that can cause Acute respiratory infections. Methods This study evaluated the presence of 14 non-influenza respiratory viruses in 872 pharyngeal exudate samples using RT-qPCR. All samples met the operational definition of a probable case of an influenza-like illness or severe acute respiratory infection and had a previous negative result for influenza by RT-qPCR. Results The presence of at least one non-influenza virus was observed in 312 samples (35.8%). The most frequent viruses were rhinovirus (RV; 33.0%), human respiratory syncytial virus (HRSV; 30.8%) and human metapneumovirus (HMPV; 10.6%). A total of 56 cases of coinfection (17.9%) caused by 2, 3, or 4 viruses were identified. Approximately 62.5% of all positive cases were in children under 9 years of age.

Immunobiology, 2016

The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids ... more The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156) were genotyped by 5' exonuclease TaqMan assays in a group of 338 patients with T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant 1(codom1), dominant (dom) and additive (add) models adjusted by age, gender, body mass index (BMI), smoking habit, and hypertension, the rs876018T allele was associated with increased risk of MetS [Odds Ratio (OR)=1.66, Pcodom1=0.005; OR=1.67, Pdom=0.003; OR=1.49, Padd=0.005] as compared to controls. On the other hand, under several models adjusted by the same variables, the rs3753827A (OR=1.52, Pcodom1=0.039 and OR=1.49, Pdom=0.039) and rs11573156C alleles (OR=6.46, Pcodom1=0.013; OR=6.70, Pcodom2=0.009; OR=6.65, Pdom=0.009) were associated with increased risk of T2DM when compared with controls. In addition, the rs876018T allele was associated with hypercholesterolemia (Pdom=0.017, Padd=0.009) and risk of subclinical atherosclerosis (SA) (Pdom=0.041) in MetS when compared with controls. Also, this allele was associated with SA in T2DM patients (Pdom=0.007). The TAG haplotype was significantly associated with increased risk of MetS (OR=1.54, P=0.006). Results suggest that PLA2G2A polymorphisms are involved in the risk of developing MetS and T2D and are associated with SA in this group of patients.

PloS one, 2017

The effect of interleukin 33 (IL-33) in the inflammatory process generates significant interest i... more The effect of interleukin 33 (IL-33) in the inflammatory process generates significant interest in the potential significance of IL-33 as a biomarker for coronary artery disease (CAD). Here, our objective was to analyze whether IL-33 gene polymorphisms are associated with premature CAD in a case-control association study. Four IL-33 polymorphisms (rs7848215, rs16924144, rs16924159 and rs7044343) were genotyped by 5' exonuclease TaqMan assays in 1095 patients with premature CAD and 1118 controls. The rs7044343 T allele was significantly associated with a diminished risk of premature CAD (OR = 0.81, 95% CI: 0.69-0.97, Pdom = 0.020; OR = 0.85, 95% CI: 0.75-0.96, Padd = 0.019) and central obesity (OR = 0.74, 95% CI: 0.58-0.93, Pdom = 0.0007), respectively. When patients were divided into groups with and without type 2 diabetes mellitus (T2DM), the rs7044343 T allele was associated with a reduced risk of premature CAD in patients without (OR = 0.85, 95% CI: 0.73-0.99, Padd = 0.038) a...

Immunology letters, Jan 12, 2015

The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, prog... more The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, progression, and destabilization of atheromatous plaques and plays an essential role in postinfarction remodeling. The aim of the present study was to evaluate the role of MCP-1 gene polymorphisms as susceptibility markers for premature coronary artery disease (CAD) and cardiovascular risk factors in the Mexican population. Four MCP-1 gene polymorphisms (rs1024611, rs2857654, rs3760396, and rs1024610) were genotyped by 5' exonuclease TaqMan assays in a group of 1072 patients with premature CAD, and 1082 healthy unrelated controls (with negative calcium score by computed tomography) seeking for associations with premature CAD and other metabolic and cardiovascular risk factors using logistic regression analyses. MCP-1 polymorphism frequencies were similar in premature CAD patients and healthy controls. When the analysis included only those premature CAD patients without type 2 diabetes me...

Copyright © 2015 Irma Eloisa Monroy-Muñoz et al. This is an open access article distributed unde... more Copyright © 2015 Irma Eloisa Monroy-Muñoz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. The relevance of TBX20 gene in heart development has been demonstrated in many animal models, but there are few works that try to elucidate the effect of TBX20 mutations in human congenital heart diseases. In these studies, all missense mutations associated with atrial septal defect (ASD) were found in the DNA-binding T-box domain, none in the transcriptional activator domain. Methods. We search for TBX20 mutations in a group of patients with ASD or ventricular septal defect (VSD) using the High Resolution Melting (HRM) method and DNA sequencing. Results. We report three missense mutations (Y309D, T370O, and M395R) within the transcriptional activator domain of human TBX20 that were associated with ASD. Conclus...

Aim The role of interleukin 17A (IL-17A) in the inflammatory process has caused interest in the p... more Aim The role of interleukin 17A (IL-17A) in the inflammatory process has caused interest in the potential significance of IL-17A as a biomarker for coronary artery disease (CAD). The aim of the present study was to evaluate the role of IL-17A gene polymorphisms as susceptibility markers for CAD in the Mexican population. Methods Four IL-17A gene polymorphisms (rs8193036, rs3819024, rs2275913 and rs8193037) were genotyped by 5 ’ exonuclease TaqMan assays in a group of 900 patients with prema-ture CAD and 667 healthy controls (with negative calcium score by computed tomography), seeking associations with CAD and other metabolic and cardiovascular risk factors using lo-gistic regression analyses. Results No single IL-17A polymorphism was associated with premature CAD, however two haplo-types (CAGG and TAGA) were significantly associated with increased risk of premature

Cytokine, 2018

Interleukin 10 (IL-10) is an anti-inflammatory cytokine with a protective role in the formation a... more Interleukin 10 (IL-10) is an anti-inflammatory cytokine with a protective role in the formation and the development of the atherosclerotic plaque. The aim of the present study was to establish if IL-10 gene polymorphisms are associated with the development of premature coronary artery disease (pCAD) and cardiovascular risk factors in Mexican individuals. Three IL-10 gene polymorphisms [-592C/A (rs1800872), -819C/T (rs1800871), and -1082 A/G (rs1800896)] and IL-10 plasma levels were analyzed in 2266 individuals (1160 pCAD patients and 1106 healthy controls). Under recessive and co-dominant2 models, the -1082 A/G (rs1800896) G allele was associated with decreased risk of developing pCAD (OR = 0.572, P = 0.022 and OR = 0.567, P = 0.023). In pCAD patients, the polymorphisms were associated with hyperinsulinemia, small and dense LDLs, hypertension, and diabetes mellitus. In the control group, the polymorphisms were associated with hypertension, hyperuricemia, and small and dense LDLs. pC...

Cytokine, 2017

Interleukin IL-15 (IL-15) has been implicated in the development of coronary artery disease (CAD)... more Interleukin IL-15 (IL-15) has been implicated in the development of coronary artery disease (CAD). The aim of the present study was to evaluate the role of IL-15 gene polymorphisms as susceptibility markers for development of subclinical atherosclerosis (SA) and cardiovascular risk factors in Mexican population. Four IL-15 gene polymorphisms (rs4956403, rs3806798, rs1057972 and rs10833) were analyzed in a group of 397 individuals with SA and 1120 controls. Under different inheritance models adjusted by traditional risk factors, the rs10833 T allele was associated with increased risk of developing SA [OR = 1.42, P codom1 = 0.046; OR = 1.48, P dom = 0.021; OR = 1.43, P add = 0.014]. Under a dominant model, the rs1057972 polymorphism was associated with central obesity (P = 0.045) and fatty liver (P = 0.021), while the rs10833 polymorphism was associated with metabolic syndrome (P = 0.007) in individuals with SA. The TAC haplotype was significantly associated with a decreased risk of SA. Individuals with rs10833CC genotype exhibited higher levels of IL-15 than individuals with CT + TT genotypes. The results suggest that IL-15 polymorphisms are involved in the risk of developing SA and are associated with metabolic syndrome, central obesity and fatty liver in our study population. The rs10833 polymorphism could be involved in regulating IL-15 production in SA.

Mediators of Inflammation, 2017

Interleukin 35 (IL-35) is a heterodimeric cytokine involved in the development of atherosclerosis... more Interleukin 35 (IL-35) is a heterodimeric cytokine involved in the development of atherosclerosis. The aim of the present study was to establish if the polymorphisms ofIL-12AandEBI3genes that encode the IL-35 subunits are associated with the development of premature coronary artery disease (CAD) in Mexican individuals. TheIL-12AandEBI3polymorphisms were determined in 1162 patients with premature CAD and 873 controls. Under different models, theEBI3rs428253 (OR = 0.831,Padd= 0.036; OR = 0.614,Prec= 0.033; OR = 0.591,Pcod2= 0.027) andIL-12Ars2243115 (OR = 0.674,Padd= 0.010; OR = 0.676,Pdom= 0.014; OR = 0.698,Phet= 0.027; OR = 0.694,Pcod1= 0.024) polymorphisms were associated with decreased risk of developing premature CAD. Some polymorphisms were associated with clinical and metabolic parameters. Significant different levels of IL-35 were observed inEBI3rs4740 and rs4905 genotypes only in the group of healthy controls. In summary, our study suggests that theEBI3andIL-12Apolymorphisms ...

Experimental and Molecular Pathology, 2017

The receptor-interacting protein 2 (Rip2) is a serine/threonine kinase involved in multiple nucle... more The receptor-interacting protein 2 (Rip2) is a serine/threonine kinase involved in multiple nuclear factor-κB (NFκB) activation pathways and is a key regulator of cellular lipid metabolism and cardiovascular disease. The aim of the present study was to evaluate the role of RIP2 gene polymorphisms as susceptibility markers for subclinical atherosclerosis (SA). Using an informatics analysis, four RIP2 gene polymorphisms with predicted functional effects (rs2293808, rs43133, rs431264, and rs16900627) were selected. The polymorphisms were genotyped in 405 individuals with SA (calcium score N 0 assessed by computed tomography) and 1099 controls (calcium score = 0). Clinical, anthropometric, tomographic and biochemical traits were measured. The association between the RIP2 polymorphisms and SA was evaluated using logistic regression analyses. Pair wise linkage disequilibrium (LD, D′) estimations between polymorphisms and haplotype reconstruction were performed with Haploview version 4:1. Under different models adjusted by age, gender, body mass index, hypertension, diabetes mellitus, smoking habit, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels, rs43133 (OR = 1.43, 95% CI: 1.05-1.94, P = 0.022), and rs16900627 (OR = 1.59, 95% CI: 1.00-2.54, P dom = 0.048 and OR = 1.60, 95% CI: 1.05-2.54, P add = 0.028) were associated with increased risk of developing SA. Moreover, rs2293808, and rs431264 were associated with clinical or metabolic parameters in SA individuals and in healthy controls. The four polymorphisms were in high linkage disequilibrium and the GAAG haplotype was associated with increased risk of developing SA (OR = 1.47, P = 0.027). This study shows for the first time, that RIP2 polymorphisms are associated with increased risk of SA and with some clinical and metabolic parameters.

Global Heart, 2016

3%). Majority of the PCI (60-80%) were elective cases. There is an increasing trend of number of ... more 3%). Majority of the PCI (60-80%) were elective cases. There is an increasing trend of number of procedures in January 2014 (n¼483) and June 2014 (n¼561). Programme costs varied considerably across all facilities, and consumables alone contribute an average 69.41%, with median RM 8,437.82 (RM 7,566.98-13,070.58). The estimated costs of PCI in this study, median RM 13,876.67 (RM11,518.00-15,025.04). Significantly lower costing is found in hospital which performed more numbers of elective cases in daycare. The overall inhospital all-cause mortality (including emergency cases) was 3.2% (n¼57) from January until June 2014. The discrepancy of mortality rate was mainly contributed by the emergency PCI cases. Conclusion: The six selected public, institution and teaching hospitals showed an increased number of PCI procedures performed in midyear as compared to earlier part of the year. The overall in-hospital all-cause mortality remained acceptably low but the scarcity of operational cost is non-related factor.

BioMed Research International, 2015

Background. The relevance ofTBX20gene in heart development has been demonstrated in many animal m... more Background. The relevance ofTBX20gene in heart development has been demonstrated in many animal models, but there are few works that try to elucidate the effect ofTBX20mutations in human congenital heart diseases. In these studies, all missense mutations associated with atrial septal defect (ASD) were found in the DNA-binding T-box domain, none in the transcriptional activator domain.Methods. We search forTBX20mutations in a group of patients with ASD or ventricular septal defect (VSD) using the High Resolution Melting (HRM) method and DNA sequencing.Results. We report three missense mutations (Y309D, T370O, and M395R) within the transcriptional activator domain of human TBX20 that were associated with ASD.Conclusions. This is the first association of TBX20 transcriptional activator domain missense mutations with ASD. These findings could have implications for diagnosis, genetic screening, and patient follow-up.

Experimental and Molecular Pathology, 2014

The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of d... more The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing in-stent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5' exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR=1.31, 95% CI: 1.04-1.66, P=0.018) and decreased frequencies of GAGATG (OR=0.47, 95% CI: 0.25-0.88, P=0.011) and AGAGCA (OR=0.15, 95% CI: 0.02-0.65, P=0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.

Nephrology, 2010

The TGF-β gene participates in the development of chronic kidney disease. We investigated whether... more The TGF-β gene participates in the development of chronic kidney disease. We investigated whether the 869 T > C, 915 G > C and -800 G > A polymorphisms of TGF-β1 are associated with diabetic nephropathy (DN). Polymorphisms were genotyped in 439 type 2 diabetes mellitus patients, 233 with diabetic nephropathy (DN+) and 206 without (DN-). The sample was characterized for relevant clinical and biochemical parameters. The 869 T > C (P = 0.016; odds ratio (OR) = 1.818, 95% confidence interval (CI) = 1.128-2.930) and the 915 G > C polymorphisms (P = 0.008, OR = 4.073, 95% CI = 1.355-12.249) were associated with diabetic nephropathy. The 869 T > C variant was associated with total cholesterol levels: CC + CT genotypes had a mean cholesterol concentration of 5.62 ± 1.40 mmol/L vs a mean concentration of 5.15 ± 1.40 mmol/L for the TT genotype (P = 0.011). Triglycerides were also higher in CC + CT genotypes (2.49 ± 1.56 mmol/L) in comparison with TT homozygotes (2.1 ± 1.22 mmol/L, P = 0.042). Multivariate logistic regression showed that the polymorphisms 869 T…

Journal of Translational Medicine, 2013

Background The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition ... more Background The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence. Methods We carried out a case–control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts. Results We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcor...

Diabetes/Metabolism Research and Reviews, 2010

Background Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors.... more Background Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors. Metabolic syndrome (MS) increases the risk of cardiovascular disease and diabetes. We analysed 14 cases of polymorphisms located in 10 candidate loci, in a sample of patients with T2D and controls from Mexico City. Methods We analysed the association of 14 polymorphisms located within 10 genes (TCF7L2, ENPP1, ADRB3, KCNJ11, LEPR, PPARγ , FTO, CDKAL1, SIRT1 and HHEX) with T2D and MS. The analysis included 519 subjects with T2D defined according to the ADA criteria, 389 with MS defined according to the AHA/NHLBI criteria and 547 controls. Association was tested with the program ADMIXMAP including individual ancestry, age, sex, education and in some cases body mass index (BMI), in a logistic regression model. Results The two markers located within the TCF7L2 gene showed strong associations with T2D (rs7903146, T allele, odd ratio (OR) = 1.76, p = 0.001 and rs12255372, T allele, OR = 1.78, p = 0.002), but did not show significant association with MS. The non-synonymous rs4994 polymorphism of the ADRB3 gene was associated with T2D (Trp allele, OR = 0.62, p = 0.001) and MS (Trp allele, OR = 0.74, p = 0.018). Nominally significant associations were also observed between T2D and the SIRT1 rs3758391 SNP and MS and the HHEX rs5015480 polymorphism. Conclusions Variants located within the gene TCF7L2 are strongly associated with T2D but not with MS, providing support to previous evidence indicating that polymorphisms at the TCF7L2 gene increase T2D risk. In contrast, the non-synonymous ADRB3 rs4994 polymorphism is associated with T2D and MS.

Immunologic Research, 2017

The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-I... more The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR'3 G37562-C (rs10754558)] were genotyped by 5' exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08-2.86, P Res = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07-2.85, P Res = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR'3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22-0.92, P Co-dom = 0.006; OR = 0.61, 95%CI 0.44-0.84, P Dom = 0.002; OR = 0.67, 95%CI 0.48-0.94, P Over-dom = 0.02; and OR = 0.65, 95%CI 0.50-0.94, P Add = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR'3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.

Written Communication, 2000

The issues of authentic context and authoritative ethos are explored through a study of a graduat... more The issues of authentic context and authoritative ethos are explored through a study of a graduate student learning to write for mathematics within the context of an English for academic purposes (EAP) course. The student faced conflicts about audience, purpose, and content knowledge as she was required to write math texts within what she perceived was an inauthentic context, an English as a second language (ESL) course. She questioned the purpose of the writing tasks as well as why an ESL instructor was teaching her to write for math, and she addressed the conflicts by writing for the instructor's discourse community and expectations, rather than her own, to earn a grade for the course. The text the student created was thus inauthentic within her own discourse community and lacked her voice of authority. These findings question the validity of EAP courses and raise several issues, especially in terms of the transferability of skills from EAP to content courses.

PLOS ONE, 2017

Background Acute respiratory infections are the leading cause of morbidity and mortality worldwid... more Background Acute respiratory infections are the leading cause of morbidity and mortality worldwide. Although a viral aetiological agent is estimated to be involved in up to 80% of cases, the majority of these agents have never been specifically identified. Since 2009, diagnostic and surveillance efforts for influenza virus have been applied worldwide. However, insufficient epidemiological information is available for the many other respiratory viruses that can cause Acute respiratory infections. Methods This study evaluated the presence of 14 non-influenza respiratory viruses in 872 pharyngeal exudate samples using RT-qPCR. All samples met the operational definition of a probable case of an influenza-like illness or severe acute respiratory infection and had a previous negative result for influenza by RT-qPCR. Results The presence of at least one non-influenza virus was observed in 312 samples (35.8%). The most frequent viruses were rhinovirus (RV; 33.0%), human respiratory syncytial virus (HRSV; 30.8%) and human metapneumovirus (HMPV; 10.6%). A total of 56 cases of coinfection (17.9%) caused by 2, 3, or 4 viruses were identified. Approximately 62.5% of all positive cases were in children under 9 years of age.

Immunobiology, 2016

The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids ... more The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156) were genotyped by 5' exonuclease TaqMan assays in a group of 338 patients with T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant 1(codom1), dominant (dom) and additive (add) models adjusted by age, gender, body mass index (BMI), smoking habit, and hypertension, the rs876018T allele was associated with increased risk of MetS [Odds Ratio (OR)=1.66, Pcodom1=0.005; OR=1.67, Pdom=0.003; OR=1.49, Padd=0.005] as compared to controls. On the other hand, under several models adjusted by the same variables, the rs3753827A (OR=1.52, Pcodom1=0.039 and OR=1.49, Pdom=0.039) and rs11573156C alleles (OR=6.46, Pcodom1=0.013; OR=6.70, Pcodom2=0.009; OR=6.65, Pdom=0.009) were associated with increased risk of T2DM when compared with controls. In addition, the rs876018T allele was associated with hypercholesterolemia (Pdom=0.017, Padd=0.009) and risk of subclinical atherosclerosis (SA) (Pdom=0.041) in MetS when compared with controls. Also, this allele was associated with SA in T2DM patients (Pdom=0.007). The TAG haplotype was significantly associated with increased risk of MetS (OR=1.54, P=0.006). Results suggest that PLA2G2A polymorphisms are involved in the risk of developing MetS and T2D and are associated with SA in this group of patients.

PloS one, 2017

The effect of interleukin 33 (IL-33) in the inflammatory process generates significant interest i... more The effect of interleukin 33 (IL-33) in the inflammatory process generates significant interest in the potential significance of IL-33 as a biomarker for coronary artery disease (CAD). Here, our objective was to analyze whether IL-33 gene polymorphisms are associated with premature CAD in a case-control association study. Four IL-33 polymorphisms (rs7848215, rs16924144, rs16924159 and rs7044343) were genotyped by 5' exonuclease TaqMan assays in 1095 patients with premature CAD and 1118 controls. The rs7044343 T allele was significantly associated with a diminished risk of premature CAD (OR = 0.81, 95% CI: 0.69-0.97, Pdom = 0.020; OR = 0.85, 95% CI: 0.75-0.96, Padd = 0.019) and central obesity (OR = 0.74, 95% CI: 0.58-0.93, Pdom = 0.0007), respectively. When patients were divided into groups with and without type 2 diabetes mellitus (T2DM), the rs7044343 T allele was associated with a reduced risk of premature CAD in patients without (OR = 0.85, 95% CI: 0.73-0.99, Padd = 0.038) a...

Immunology letters, Jan 12, 2015

The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, prog... more The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, progression, and destabilization of atheromatous plaques and plays an essential role in postinfarction remodeling. The aim of the present study was to evaluate the role of MCP-1 gene polymorphisms as susceptibility markers for premature coronary artery disease (CAD) and cardiovascular risk factors in the Mexican population. Four MCP-1 gene polymorphisms (rs1024611, rs2857654, rs3760396, and rs1024610) were genotyped by 5' exonuclease TaqMan assays in a group of 1072 patients with premature CAD, and 1082 healthy unrelated controls (with negative calcium score by computed tomography) seeking for associations with premature CAD and other metabolic and cardiovascular risk factors using logistic regression analyses. MCP-1 polymorphism frequencies were similar in premature CAD patients and healthy controls. When the analysis included only those premature CAD patients without type 2 diabetes me...