Marisol López-López - Academia.edu (original) (raw)
Papers by Marisol López-López
Genes
Parkinson’s disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, a... more Parkinson’s disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, and aging as its biggest risk factors. Mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) are biological aging markers with inconclusive results regarding their association with PD. A case–control study was used to measure TL and mtDNA-CN using qPCR in PBMCs. PD patients were naive at baseline (T0) and followed-up at one (T1) and two (T2) years after the dopaminergic treatment (DRT). Plasmatic cytokines were determined by ELISA in all participants, along with clinical parameters of patients at T0. While TL was shorter in patients vs. controls at all time points evaluated (p < 0.01), mtDNA-CN showed no differences. An increase in mtDNA-CN and TL was observed in treated patients vs. naive ones (p < 0.001). Our statistical model analyzed both aging markers with covariates, showing a strong correlation between them (r = 0.57, p < 0.01), and IL-17A levels positively cor...
Drug Development Research, Dec 17, 2020
Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treat... more Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treatment. However, there is little information regarding pharmacogenetics of CLZ in patients with refractory psychosis and its clinical correlation with alcohol intake. Although neurological effects of CLZ in patients with concomitant alcohol intake are documented, its use is very common in patients with psychosis. We explored the impact of CYP1A2, CYP2D6, CYP2C19, and CYP3A4 genetic variants on CLZ pharmacokinetics and side effects, along with coffee/alcohol/tobacco consumption habits and clinical data of 48 adult patients with refractory psychosis on CLZ antipsychotic monotherapy. Relevant CYP variants in CLZ metabolism were evaluated by targeted genotyping and multiplex ligation-dependent probe amplification. CLZ and its main metabolite plasma concentrations were determined by high performance liquid chromatography. Biochemical and molecular data, along with other potential confounders, were included in the analysis by linear regression. Overall, CYP variants showed no effect on CLZ pharmacokinetics. The rs2069514 variant in homozygous genotype (also known as CYP1A2*1C/*1C) was associated with CLZ adverse reactions in Mexican patients with refractory psychosis (OR = 3.55 CI 95 = 1.041-12.269, p = .043) and demonstrated that this effect is doubled by concomitant alcohol consumption (OR = 7.9 CI 95 = 1.473-42.369, p = .016). Clinicians should be aware of this information before starting CLZ use, when treating patients with refractory psychosis, who are alcohol drinkers and carriers of this genetic variant in order to prevent CLZ-related adverse reactions. Nevertheless, our findings should be replicated in larger samples.
Archives of Medical Research, Nov 1, 2012
Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) is the most frequent cause of dementia in the elderly and represents an important and increasing clinical challenge in terms of diagnosis and treatment. This review highlights the role of genetics in understanding the pieces of the complex AD puzzle and summarizes the genes known to be involved in Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. The amount of risk of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease that is attributable to genetics is estimated to be ∼70%. Mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) are responsible for early-onset autosomal dominant AD. Although mutations in these genes account for ∼1% of AD cases, their identification has been crucial to understand the molecular mechanisms of AD. For the more common complex late-onset AD, the ɛ-4 allele of the gene encoding apolipoprotein E (APOE) has been recognized as a major genetic risk factor. More recently, several potential disease risk genes have been identified with the use of advanced genomic methods like genome-wide association studies (GWAS). In the end, the knowledge of the pathophysiological mechanisms leading to AD will enable the development of more accurate diagnostic tests and new disease-treating strategies.
Environmental Pollution, Feb 1, 2021
A vast amount of evidence indicates that bisphenol A (BPA) and phthalates are widely distributed ... more A vast amount of evidence indicates that bisphenol A (BPA) and phthalates are widely distributed in the environment since these compounds are mass-produced for the manufacture of plastics and plasticizers. These compounds belong to a large group of substances termed endocrine-disrupting chemicals (EDC). It is well known that humans and living organisms are unavoidably and unintentionally exposed to BPA and phthalates from food packaging materials and many other everyday products. BPA and phthalates exert their effect by interfering with hormone synthesis, bioavailability, and action, thereby altering cellular proliferation and differentiation, tissue development, and the regulation of several physiological processes. In fact, these EDC can alter fetal programming at an epigenetic level, which can be transgenerational transmitted and may be involved in the development of various chronic pathologies later in the adulthood, including metabolic, reproductive and degenerative diseases, and certain types of cancer. In this review, we describe the most recent proposed mechanisms of action of these EDC and offer a compelling selection of experimental, epidemiological and clinical studies, which show evidence of how exposure to these pollutants affects our health during development, and their association with a wide range of reproductive, metabolic and neurological diseases, as well as hormone-related cancers. We stress the importance of concern in the general population and the urgent need for the medical health care system to closely monitor EDC levels in the population due to unavoidable and involuntary exposure to these pollutants and their impact on human health.
Neurologia, May 1, 2022
Conclusiones: Se han identificado posibles biomarcadores farmacogenéticos para el tratamiento de ... more Conclusiones: Se han identificado posibles biomarcadores farmacogenéticos para el tratamiento de EA; sin embargo, se requieren más estudios farmacogenéticos en otras poblaciones que no han sido investigadas, así como profundizar en la identificación de los biomarcadores. Este conocimiento podría ayudar a predecir la respuesta a fármacos modificadores de EA y contribuiría a tomar mejores decisiones en el tratamiento de la enfermedad en un contexto tan complejo como es el envejecimiento.
Brazilian Journal of Psychiatry
Archives of Medical Research
BACKGROUND Cognitive impairment in schizophrenia (SCZ) is a core feature, relevant for the diseas... more BACKGROUND Cognitive impairment in schizophrenia (SCZ) is a core feature, relevant for the disease prognosis and functional capacity of the patients. It has also been identified as an endophenotype and proposed as a genetic mechanism of risk for schizophrenia. AIM OF THE STUDY We aimed to evaluate the association of genetic variants in COMT, PRODH, and DISC1 with the cognitive performance of Mexican-Mestizo adult patients with SCZ in order to identify endophenotypes. SUBJECTS AND METHODS The association of seven variants in COMT, 15 in PRODH, and three in DISC1 was evaluated in 150 patients and 150 control volunteers. The MATRICS Consensus Cognitive Battery was administered to a subset of 44 patients and 42 controls. RESULTS COMT rs4633 was related to MATRICS global assessment, while in the multi-phenotype analysis, PRODH rs2870984 was associated with processing speed, working memory, verbal learning, and social cognition. In addition, the association of variants in COMT and PRODH with the risk for SCZ was also found in Mexican-Mestizo patients. CONCLUSION COMT might be a potential biomarker of cognitive impairment in Mexican-Mestizo patients with SCZ, supporting the relevance of this gene for drug design.
European Neuropsychopharmacology, 2021
Parkinsonism & Related Disorders, 2020
background: Prior studies have suggested the presence of a relation between obesity and ventricul... more background: Prior studies have suggested the presence of a relation between obesity and ventricular repolarization. These studies showed prolongation of the QTc interval (QTc) and greater QT or QTc dispersion (QTd) with increased body weight indices. Methods: A comprehensive literature search was conducted with the electronic databases MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). These were queried to identify controlled studies investigating QTc, QTd and obesity. Two independent reviewers selected studies and extracted data. Fixed-effects meta-analysis method was used to pool outcomes across studies calculating mean difference (MD) for both QTc and QTd with 95% confidence intervals (CI) comparing obese and non-obese subjects. Units were measured in milliseconds. results: A total of thirteen original studies fulfilled the inclusion criteria enrolling 7153 patients. Patient demographics were obtained in addition to baseline characteristics including body mass index, study design, sample size, QTc and QTd. Compared to controls, there was a significant longer QTc in obese compared to non-obese subjects with a mean difference of 21.51 milliseconds . QTd was also significantly longer in obese subjects with a mean difference of 17.99 milliseconds (95% CI: 19.66 -16.31) when compared to non-obese persons. Obesity is associated with significantly longer QTc and QTd. This indicates the presence of a strong relation between obesity and ventricular repolarization.
Journal of the European Academy of Dermatology and Venereology : JEADV, Jan 3, 2017
Hypohidrotic ectodermal dysplasia (HED) has a prevalence of 1:5,000-10,000 newborns and it is cha... more Hypohidrotic ectodermal dysplasia (HED) has a prevalence of 1:5,000-10,000 newborns and it is characterized by hypotrichosis and abnormalities in teeth and sweat glands.(1) Most patients have an X-linked (XLHED) pattern of inheritance due to mutations in EDA which encodes for ectodysplasin. In addition, three HED-associated autosomal genes are known: EDAR which encodes for an ectodysplasin receptor; EDARADD corresponding to a cytoplasmic adaptor molecule and WNT10A which encodes for a signaling molecule of the WNT/β-catenin pathway.(1-4) This article is protected by copyright. All rights reserved.
Drug Development Research, 2020
Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treat... more Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treatment. However, there is little information regarding pharmacogenetics of CLZ in patients with refractory psychosis and its clinical correlation with alcohol intake. Although neurological effects of CLZ in patients with concomitant alcohol intake are documented, its use is very common in patients with psychosis. We explored the impact of CYP1A2, CYP2D6, CYP2C19, and CYP3A4 genetic variants on CLZ pharmacokinetics and side effects, along with coffee/alcohol/tobacco consumption habits and clinical data of 48 adult patients with refractory psychosis on CLZ antipsychotic monotherapy. Relevant CYP variants in CLZ metabolism were evaluated by targeted genotyping and multiplex ligation‐dependent probe amplification. CLZ and its main metabolite plasma concentrations were determined by high performance liquid chromatography. Biochemical and molecular data, along with other potential confounders, w...
Frontiers in Psychiatry
Long-term studies have shown significantly lower mortality rates in patients with continuous cloz... more Long-term studies have shown significantly lower mortality rates in patients with continuous clozapine (CLZ) treatment than other antipsychotics. We aimed to evaluate epigenetic age and DNA methylome differences between CLZ-treated patients and those without psychopharmacological treatment. The DNA methylome was analyzed using the Infinium MethylationEPIC BeadChip in 31 CLZ-treated patients with psychotic disorders and 56 patients with psychiatric disorders naive to psychopharmacological treatment. Delta age (Δage) was calculated as the difference between predicted epigenetic age and chronological age. CLZ-treated patients were stratified by sex, age, and years of treatment. Differential methylation sites between both groups were determined using linear regression models. The Δage in CLZ-treated patients was on average lower compared with drug-naive patients for the three clocks analyzed; however, after data-stratification, this difference remained only in male patients. Additional ...
Pharmacogenomics, Apr 1, 2022
Clozapine (CLZ) is an atypical antipsychotic reserved for patients with refractory psychosis, but... more Clozapine (CLZ) is an atypical antipsychotic reserved for patients with refractory psychosis, but it is associated with a significant risk of severe adverse reactions (ADRs) that are potentiated with the concomitant use of alcohol. Additionally, pharmacogenetic studies have explored the influence of several genetic variants in CYP450, receptors and transporters involved in the interindividual response to CLZ. Herein, we systematically review the current multiomics knowledge behind the interaction between CLZ and alcohol intake, and how its concomitant use might modulate the pharmacogenetics. CYP1A2*1F, *1C and other alleles not yet discovered could support a precision medicine approach for better therapeutic effects and fewer CLZ ADRs. CLZ monitoring systems should be amended and include alcohol intake to protect patients from severe CLZ ADRs.
Molecular Psychiatry, Dec 4, 2012
Dermatologica Sinica
X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by EDA pathogenic variants. Female c... more X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by EDA pathogenic variants. Female carriers show several clinical manifestations in variable percentages. We studied 11 Mexican heterozygous females with an EDA variant. The most frequent symptoms were similar to previous reports; however, two females (18%) reported dry eye syndrome, data rarely explored in carriers. The penetrance was 91% with clinical variability that might be related to the location of the mutation and/or to a skewed X-inactivation pattern. Our results highlight the importance of offering molecular testing to potential female carriers and support XLHED as an X-linked entity with incomplete penetrance in females.
Pharmaceuticals, 2021
Clozapine (CLZ) is the only antipsychotic drug that has been proven to be effective in patients w... more Clozapine (CLZ) is the only antipsychotic drug that has been proven to be effective in patients with refractory psychosis, but it has also been proposed as an effective mood stabilizer; however, the complex mechanisms of action of CLZ are not yet fully known. To find predictors of CLZ-associated phenotypes (i.e., the metabolic ratio, dosage, and response), we explore the genomic and epigenomic characteristics of 44 patients with refractory psychosis who receive CLZ treatment based on the integration of polygenic risk score (PRS) analyses in simultaneous methylome profiles. Surprisingly, the PRS for bipolar disorder (BD-PRS) was associated with the CLZ metabolic ratio (pseudo-R2 = 0.2080, adjusted p-value = 0.0189). To better explain our findings in a biological context, we assess the protein–protein interactions between gene products with high impact variants in the top enriched pathways and those exhibiting differentially methylated sites. The GABAergic synapse pathway was found to...
Frontiers in Oncology, 2020
Retinol plays a significant role in several physiological processes through their nuclear recepto... more Retinol plays a significant role in several physiological processes through their nuclear receptors, whose expression depends on retinol cytoplasmic concentration. Loss of expression of nuclear receptors and low retinol levels have been correlated with lung cancer development. Stimulated by retinoic acid 6 (STRA6) is the only described cell membrane receptor for retinol uptake. Some chronic diseases have been linked with specific polymorphisms in STRA6. This study aimed to evaluate four STRA6 single nucleotide polymorphisms (SNPs) (rs4886578, rs736118, rs351224, and rs97445) among 196 patients with locally-advanced and metastatic non-small cell lung cancer (NSCLC) patients. Genotyping, through a validated SNP assay and determined using real time-PCR, was correlated with clinical features and outcomes. NSCLC patients with a TT SNP rs4886578 and rs736118 genotype were more likely to be >60 years, non-smokers, and harboring EGFR mutations. Patients with a TT genotype compared with a...
Pharmacogenomics, 2021
Aim: We evaluated the potential influence of genetic ( CYP3A5, EPHX1, NR1I2, HNF4A, ABCC2, RALBP1... more Aim: We evaluated the potential influence of genetic ( CYP3A5, EPHX1, NR1I2, HNF4A, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1) and nongenetic factors on carbamazepine (CBZ) response, adverse drug reactions and CBZ plasma concentrations in 126 Mexican Mestizos (MM) with epilepsy. Subjects & methods: Patients were genotyped for 27 variants using TaqMan®assays. Results: CBZ response was associated with NR1I2 variants and lamotrigine cotreatment. CBZ-induced adverse drug reactions were related to antiepileptic polytherapy and SCN1A rs2298771/rs3812718 haplotype. CBZ plasma concentrations were influenced by NR1I2-rs2276707 and -rs3814058, and by phenytoin cotreatment. CBZ daily dose was also influenced by NR1I2-rs3814055 and EPHX1-rs1051740. Conclusion: Interindividual variability in CBZ treatment was partly explained by NR1I2, EPHX1 and SCN1A variants, as well as antiepileptic cotreatment in MM with epilepsy.
Genes
Parkinson’s disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, a... more Parkinson’s disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, and aging as its biggest risk factors. Mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) are biological aging markers with inconclusive results regarding their association with PD. A case–control study was used to measure TL and mtDNA-CN using qPCR in PBMCs. PD patients were naive at baseline (T0) and followed-up at one (T1) and two (T2) years after the dopaminergic treatment (DRT). Plasmatic cytokines were determined by ELISA in all participants, along with clinical parameters of patients at T0. While TL was shorter in patients vs. controls at all time points evaluated (p < 0.01), mtDNA-CN showed no differences. An increase in mtDNA-CN and TL was observed in treated patients vs. naive ones (p < 0.001). Our statistical model analyzed both aging markers with covariates, showing a strong correlation between them (r = 0.57, p < 0.01), and IL-17A levels positively cor...
Drug Development Research, Dec 17, 2020
Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treat... more Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treatment. However, there is little information regarding pharmacogenetics of CLZ in patients with refractory psychosis and its clinical correlation with alcohol intake. Although neurological effects of CLZ in patients with concomitant alcohol intake are documented, its use is very common in patients with psychosis. We explored the impact of CYP1A2, CYP2D6, CYP2C19, and CYP3A4 genetic variants on CLZ pharmacokinetics and side effects, along with coffee/alcohol/tobacco consumption habits and clinical data of 48 adult patients with refractory psychosis on CLZ antipsychotic monotherapy. Relevant CYP variants in CLZ metabolism were evaluated by targeted genotyping and multiplex ligation-dependent probe amplification. CLZ and its main metabolite plasma concentrations were determined by high performance liquid chromatography. Biochemical and molecular data, along with other potential confounders, were included in the analysis by linear regression. Overall, CYP variants showed no effect on CLZ pharmacokinetics. The rs2069514 variant in homozygous genotype (also known as CYP1A2*1C/*1C) was associated with CLZ adverse reactions in Mexican patients with refractory psychosis (OR = 3.55 CI 95 = 1.041-12.269, p = .043) and demonstrated that this effect is doubled by concomitant alcohol consumption (OR = 7.9 CI 95 = 1.473-42.369, p = .016). Clinicians should be aware of this information before starting CLZ use, when treating patients with refractory psychosis, who are alcohol drinkers and carriers of this genetic variant in order to prevent CLZ-related adverse reactions. Nevertheless, our findings should be replicated in larger samples.
Archives of Medical Research, Nov 1, 2012
Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) is the most frequent cause of dementia in the elderly and represents an important and increasing clinical challenge in terms of diagnosis and treatment. This review highlights the role of genetics in understanding the pieces of the complex AD puzzle and summarizes the genes known to be involved in Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. The amount of risk of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease that is attributable to genetics is estimated to be ∼70%. Mutations in the genes encoding amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) are responsible for early-onset autosomal dominant AD. Although mutations in these genes account for ∼1% of AD cases, their identification has been crucial to understand the molecular mechanisms of AD. For the more common complex late-onset AD, the ɛ-4 allele of the gene encoding apolipoprotein E (APOE) has been recognized as a major genetic risk factor. More recently, several potential disease risk genes have been identified with the use of advanced genomic methods like genome-wide association studies (GWAS). In the end, the knowledge of the pathophysiological mechanisms leading to AD will enable the development of more accurate diagnostic tests and new disease-treating strategies.
Environmental Pollution, Feb 1, 2021
A vast amount of evidence indicates that bisphenol A (BPA) and phthalates are widely distributed ... more A vast amount of evidence indicates that bisphenol A (BPA) and phthalates are widely distributed in the environment since these compounds are mass-produced for the manufacture of plastics and plasticizers. These compounds belong to a large group of substances termed endocrine-disrupting chemicals (EDC). It is well known that humans and living organisms are unavoidably and unintentionally exposed to BPA and phthalates from food packaging materials and many other everyday products. BPA and phthalates exert their effect by interfering with hormone synthesis, bioavailability, and action, thereby altering cellular proliferation and differentiation, tissue development, and the regulation of several physiological processes. In fact, these EDC can alter fetal programming at an epigenetic level, which can be transgenerational transmitted and may be involved in the development of various chronic pathologies later in the adulthood, including metabolic, reproductive and degenerative diseases, and certain types of cancer. In this review, we describe the most recent proposed mechanisms of action of these EDC and offer a compelling selection of experimental, epidemiological and clinical studies, which show evidence of how exposure to these pollutants affects our health during development, and their association with a wide range of reproductive, metabolic and neurological diseases, as well as hormone-related cancers. We stress the importance of concern in the general population and the urgent need for the medical health care system to closely monitor EDC levels in the population due to unavoidable and involuntary exposure to these pollutants and their impact on human health.
Neurologia, May 1, 2022
Conclusiones: Se han identificado posibles biomarcadores farmacogenéticos para el tratamiento de ... more Conclusiones: Se han identificado posibles biomarcadores farmacogenéticos para el tratamiento de EA; sin embargo, se requieren más estudios farmacogenéticos en otras poblaciones que no han sido investigadas, así como profundizar en la identificación de los biomarcadores. Este conocimiento podría ayudar a predecir la respuesta a fármacos modificadores de EA y contribuiría a tomar mejores decisiones en el tratamiento de la enfermedad en un contexto tan complejo como es el envejecimiento.
Brazilian Journal of Psychiatry
Archives of Medical Research
BACKGROUND Cognitive impairment in schizophrenia (SCZ) is a core feature, relevant for the diseas... more BACKGROUND Cognitive impairment in schizophrenia (SCZ) is a core feature, relevant for the disease prognosis and functional capacity of the patients. It has also been identified as an endophenotype and proposed as a genetic mechanism of risk for schizophrenia. AIM OF THE STUDY We aimed to evaluate the association of genetic variants in COMT, PRODH, and DISC1 with the cognitive performance of Mexican-Mestizo adult patients with SCZ in order to identify endophenotypes. SUBJECTS AND METHODS The association of seven variants in COMT, 15 in PRODH, and three in DISC1 was evaluated in 150 patients and 150 control volunteers. The MATRICS Consensus Cognitive Battery was administered to a subset of 44 patients and 42 controls. RESULTS COMT rs4633 was related to MATRICS global assessment, while in the multi-phenotype analysis, PRODH rs2870984 was associated with processing speed, working memory, verbal learning, and social cognition. In addition, the association of variants in COMT and PRODH with the risk for SCZ was also found in Mexican-Mestizo patients. CONCLUSION COMT might be a potential biomarker of cognitive impairment in Mexican-Mestizo patients with SCZ, supporting the relevance of this gene for drug design.
European Neuropsychopharmacology, 2021
Parkinsonism & Related Disorders, 2020
background: Prior studies have suggested the presence of a relation between obesity and ventricul... more background: Prior studies have suggested the presence of a relation between obesity and ventricular repolarization. These studies showed prolongation of the QTc interval (QTc) and greater QT or QTc dispersion (QTd) with increased body weight indices. Methods: A comprehensive literature search was conducted with the electronic databases MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). These were queried to identify controlled studies investigating QTc, QTd and obesity. Two independent reviewers selected studies and extracted data. Fixed-effects meta-analysis method was used to pool outcomes across studies calculating mean difference (MD) for both QTc and QTd with 95% confidence intervals (CI) comparing obese and non-obese subjects. Units were measured in milliseconds. results: A total of thirteen original studies fulfilled the inclusion criteria enrolling 7153 patients. Patient demographics were obtained in addition to baseline characteristics including body mass index, study design, sample size, QTc and QTd. Compared to controls, there was a significant longer QTc in obese compared to non-obese subjects with a mean difference of 21.51 milliseconds . QTd was also significantly longer in obese subjects with a mean difference of 17.99 milliseconds (95% CI: 19.66 -16.31) when compared to non-obese persons. Obesity is associated with significantly longer QTc and QTd. This indicates the presence of a strong relation between obesity and ventricular repolarization.
Journal of the European Academy of Dermatology and Venereology : JEADV, Jan 3, 2017
Hypohidrotic ectodermal dysplasia (HED) has a prevalence of 1:5,000-10,000 newborns and it is cha... more Hypohidrotic ectodermal dysplasia (HED) has a prevalence of 1:5,000-10,000 newborns and it is characterized by hypotrichosis and abnormalities in teeth and sweat glands.(1) Most patients have an X-linked (XLHED) pattern of inheritance due to mutations in EDA which encodes for ectodysplasin. In addition, three HED-associated autosomal genes are known: EDAR which encodes for an ectodysplasin receptor; EDARADD corresponding to a cytoplasmic adaptor molecule and WNT10A which encodes for a signaling molecule of the WNT/β-catenin pathway.(1-4) This article is protected by copyright. All rights reserved.
Drug Development Research, 2020
Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treat... more Clozapine (CLZ) is an atypical antipsychotic and the gold standard for refractory psychosis treatment. However, there is little information regarding pharmacogenetics of CLZ in patients with refractory psychosis and its clinical correlation with alcohol intake. Although neurological effects of CLZ in patients with concomitant alcohol intake are documented, its use is very common in patients with psychosis. We explored the impact of CYP1A2, CYP2D6, CYP2C19, and CYP3A4 genetic variants on CLZ pharmacokinetics and side effects, along with coffee/alcohol/tobacco consumption habits and clinical data of 48 adult patients with refractory psychosis on CLZ antipsychotic monotherapy. Relevant CYP variants in CLZ metabolism were evaluated by targeted genotyping and multiplex ligation‐dependent probe amplification. CLZ and its main metabolite plasma concentrations were determined by high performance liquid chromatography. Biochemical and molecular data, along with other potential confounders, w...
Frontiers in Psychiatry
Long-term studies have shown significantly lower mortality rates in patients with continuous cloz... more Long-term studies have shown significantly lower mortality rates in patients with continuous clozapine (CLZ) treatment than other antipsychotics. We aimed to evaluate epigenetic age and DNA methylome differences between CLZ-treated patients and those without psychopharmacological treatment. The DNA methylome was analyzed using the Infinium MethylationEPIC BeadChip in 31 CLZ-treated patients with psychotic disorders and 56 patients with psychiatric disorders naive to psychopharmacological treatment. Delta age (Δage) was calculated as the difference between predicted epigenetic age and chronological age. CLZ-treated patients were stratified by sex, age, and years of treatment. Differential methylation sites between both groups were determined using linear regression models. The Δage in CLZ-treated patients was on average lower compared with drug-naive patients for the three clocks analyzed; however, after data-stratification, this difference remained only in male patients. Additional ...
Pharmacogenomics, Apr 1, 2022
Clozapine (CLZ) is an atypical antipsychotic reserved for patients with refractory psychosis, but... more Clozapine (CLZ) is an atypical antipsychotic reserved for patients with refractory psychosis, but it is associated with a significant risk of severe adverse reactions (ADRs) that are potentiated with the concomitant use of alcohol. Additionally, pharmacogenetic studies have explored the influence of several genetic variants in CYP450, receptors and transporters involved in the interindividual response to CLZ. Herein, we systematically review the current multiomics knowledge behind the interaction between CLZ and alcohol intake, and how its concomitant use might modulate the pharmacogenetics. CYP1A2*1F, *1C and other alleles not yet discovered could support a precision medicine approach for better therapeutic effects and fewer CLZ ADRs. CLZ monitoring systems should be amended and include alcohol intake to protect patients from severe CLZ ADRs.
Molecular Psychiatry, Dec 4, 2012
Dermatologica Sinica
X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by EDA pathogenic variants. Female c... more X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by EDA pathogenic variants. Female carriers show several clinical manifestations in variable percentages. We studied 11 Mexican heterozygous females with an EDA variant. The most frequent symptoms were similar to previous reports; however, two females (18%) reported dry eye syndrome, data rarely explored in carriers. The penetrance was 91% with clinical variability that might be related to the location of the mutation and/or to a skewed X-inactivation pattern. Our results highlight the importance of offering molecular testing to potential female carriers and support XLHED as an X-linked entity with incomplete penetrance in females.
Pharmaceuticals, 2021
Clozapine (CLZ) is the only antipsychotic drug that has been proven to be effective in patients w... more Clozapine (CLZ) is the only antipsychotic drug that has been proven to be effective in patients with refractory psychosis, but it has also been proposed as an effective mood stabilizer; however, the complex mechanisms of action of CLZ are not yet fully known. To find predictors of CLZ-associated phenotypes (i.e., the metabolic ratio, dosage, and response), we explore the genomic and epigenomic characteristics of 44 patients with refractory psychosis who receive CLZ treatment based on the integration of polygenic risk score (PRS) analyses in simultaneous methylome profiles. Surprisingly, the PRS for bipolar disorder (BD-PRS) was associated with the CLZ metabolic ratio (pseudo-R2 = 0.2080, adjusted p-value = 0.0189). To better explain our findings in a biological context, we assess the protein–protein interactions between gene products with high impact variants in the top enriched pathways and those exhibiting differentially methylated sites. The GABAergic synapse pathway was found to...
Frontiers in Oncology, 2020
Retinol plays a significant role in several physiological processes through their nuclear recepto... more Retinol plays a significant role in several physiological processes through their nuclear receptors, whose expression depends on retinol cytoplasmic concentration. Loss of expression of nuclear receptors and low retinol levels have been correlated with lung cancer development. Stimulated by retinoic acid 6 (STRA6) is the only described cell membrane receptor for retinol uptake. Some chronic diseases have been linked with specific polymorphisms in STRA6. This study aimed to evaluate four STRA6 single nucleotide polymorphisms (SNPs) (rs4886578, rs736118, rs351224, and rs97445) among 196 patients with locally-advanced and metastatic non-small cell lung cancer (NSCLC) patients. Genotyping, through a validated SNP assay and determined using real time-PCR, was correlated with clinical features and outcomes. NSCLC patients with a TT SNP rs4886578 and rs736118 genotype were more likely to be >60 years, non-smokers, and harboring EGFR mutations. Patients with a TT genotype compared with a...
Pharmacogenomics, 2021
Aim: We evaluated the potential influence of genetic ( CYP3A5, EPHX1, NR1I2, HNF4A, ABCC2, RALBP1... more Aim: We evaluated the potential influence of genetic ( CYP3A5, EPHX1, NR1I2, HNF4A, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1) and nongenetic factors on carbamazepine (CBZ) response, adverse drug reactions and CBZ plasma concentrations in 126 Mexican Mestizos (MM) with epilepsy. Subjects & methods: Patients were genotyped for 27 variants using TaqMan®assays. Results: CBZ response was associated with NR1I2 variants and lamotrigine cotreatment. CBZ-induced adverse drug reactions were related to antiepileptic polytherapy and SCN1A rs2298771/rs3812718 haplotype. CBZ plasma concentrations were influenced by NR1I2-rs2276707 and -rs3814058, and by phenytoin cotreatment. CBZ daily dose was also influenced by NR1I2-rs3814055 and EPHX1-rs1051740. Conclusion: Interindividual variability in CBZ treatment was partly explained by NR1I2, EPHX1 and SCN1A variants, as well as antiepileptic cotreatment in MM with epilepsy.