Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study (original) (raw)
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Background: Genetic polymorphisms of antioxidant enzymes CAT, GPX, and SOD are involved in the etiology of obesity and its principal comorbidities. The aim of the present study was to analyze the effect of aforementioned SNPs over the output of several variables in people with obesity after a nutritional intervention. The study included 92 Mexican women, which received a dietary intervention by 3 months. Participants were genotyped and stratified into two groups: (1) carriers; mutated homozygous plus heterozygous (CR) and (2) homozygous wild type (WT). A comparison between CR and WT was done in clinical (CV), biochemical (BV), and anthropometric variables (AV), at the beginning and at the end of the intervention. Results: Participants (n = 92) showed statistically significant differences (p < 0.05) at the end of the nutritional intervention in several CV, BV, and AV. However, two kinds of responses were observed after genotyping participants: (A) CR and WT showed statistically significant differences (p < 0.05) in several CV, BV, and AV for the SNPs 599C>T GPX1 (rs1050450), − 251A>G SOD1 (rs2070424), and − 262C>T CAT (rs1001179). (B) Only CR showed statistically changes (p < 0.05) in several CV, BV, and AV for the SNPs − 21A>T CAT (rs7943316) and 47C>T SOD2 (rs4880). The dietary intervention effect was statistically significantly between the polymorphisms of 47C>T SOD2 and BMI, SBP, TBARS, total cholesterol, and C-LCL (p < 0.05) and between the polymorphisms of − 21A>T CAT (rs7943316) and SBP, DBP, total cholesterol, and atherogenic index (p < 0.05). Conclusion: People with obesity display different response in several CV, BV, and AV after a nutritional intervention, depending on the antioxidant genetic background of SOD and CAT enzymes.
The Journal of Clinical Endocrinology and Metabolism, 1999
Peroxisome proliferator-activated receptor-␥ (PPAR␥) is a nuclear receptor that regulates adipocyte differentiation. Variations in the PPAR␥ gene may affect the function of the PPAR␥ and, therefore, body adipocity. We investigated the frequencies of the Pro 12 Ala polymorphism in exon B and the silent CAC478CAT polymorphism in exon 6 of the PPAR␥ gene and their effects on body weight, body composition, and energy expenditure in obese Finns. One hundred and seventy obese subjects [29 men and 141 women; body mass index (BMI), 35.7 Ϯ 3.8 kg/m 2 ; age, 43 Ϯ 8 yr; mean Ϯ SD) participated in the study. The frequencies of the Ala 12 allele in exon B and CAT478 allele in exon 6 were not significantly different between the obese and population-based control subjects (0.14 vs. 0.13 and 0.19 vs. 0.21, respectively). The polymorphisms were associated with increased BMI [Pro 12 Pro, 34.5 Ϯ 3.8; Pro 12 Ala, 34.8 Ϯ 3.1; Ala 12 Ala, 39.2 Ϯ 4.6 kg/m 2 (P ϭ 0.011); CAC478CAC, 34.5 Ϯ 3.8; CAC478CAT, 34.5 Ϯ 3.3; CAT478CAT, 37.7 Ϯ 4.1 kg/m 2 (P ϭ 0.046)]. In addition, the women with both Ala 12 Ala and CAT478CAT genotypes (n ϭ 5) were significantly more obese compared with the women having both Pro 12 Pro and CAC478CAC genotypes (n ϭ 85; BMI, 40.6 Ϯ 3.3 vs. 34.4 Ϯ 3.9 kg/m 2 ; P ϭ 0.001), and they had increased fat mass (46.8 Ϯ 9.1 vs. 36.8 Ϯ 7.5 kg; P ϭ 0.005). In conclusion, the Pro 12 Ala and CAC478CAT polymorphisms in the PPAR␥ gene are associated with severe overweight and increased fat mass among obese women.
Association between polymorphisms in candidate genes and morbid obesity
International Journal of Obesity, 2001
Polymorphisms in a number of candidate genes have been reported to be associated with obesity. We have determined the incidence of the following polymorphisms in the following candidate genes in a group of 388 morbid obese patients (mean body mass index (BMI) 52 AE 8.01) who underwent gastric banding surgery: lipoprotein lipase (LpL) t-93 g and N291S; peroxisome proliferator receptor g (PPARg), P12A, P115Q and c1431t; peroxisome proliferator receptor a (PPARa) L162V; badrenergic receptor 2 (b-AR 2), Q27E; b-adrenergic receptor 3 (b-AR 3) W64R; uncoupling protein 1 (ucp-1), a-3826g, ucp-2, 45 bp insertion. Only for the ucp2 polymorphism did we find a statistically significant association with obesity. The b-AR 3 W64R and ucp-1 a-3826g polymorphisms influenced the rate of the development of obesity and may act synergistically.
PLoS ONE, 2013
Objective: Obesity has become a leading preventable cause of morbidity and mortality in many parts of the world. It is thought to originate from multiple genetic and environmental determinants. The aim of the current study was to introduce haplotype-based multi-locus stepwise regression (MSR) as a method to investigate combinations of unlinked single nucleotide polymorphisms (SNPs) for obesity phenotypes. Methods: In 2,122 healthy randomly selected men and women of the EPIC-Potsdam cohort, the association between 41 SNPs from 18 obesity-candidate genes and either body mass index (BMI, mean = 25.9 kg/m 2 , SD = 4.1) or waist circumference (WC, mean = 85.2 cm, SD = 12.6) was assessed. Single SNP analyses were done by using linear regression adjusted for age, sex, and other covariates. Subsequently, MSR was applied to search for the 'best' SNP combinations. Combinations were selected according to specific AIC c and p-value criteria. Model uncertainty was accounted for by a permutation test. Results: The strongest single SNP effects on BMI were found for TBC1D1 rs637797 (b = 20.33, SE = 0.13), FTO rs9939609 (b = 0.28, SE = 0.13), MC4R rs17700144 (b = 0.41, SE = 0.15), and MC4R rs10871777 (b = 0.34, SE = 0.14). All these SNPs showed similar effects on waist circumference. The two 'best' six-SNP combinations for BMI (global p-value = 3.45?10-6 and 6.82?10-6) showed effects ranging from 21.70 (SE = 0.34) to 0.74 kg/m 2 (SE = 0.21) per allele combination. We selected two six-SNP combinations on waist circumference (global p-value = 7.80?10-6 and 9.76?10-6) with an allele combination effect of 22.96 cm (SE = 0.76) at maximum. Additional adjustment for BMI revealed 15 three-SNP combinations (global p-values ranged from 3.09?10-4 to 1.02?10-2). However, after carrying out the permutation test all SNP combinations lost significance indicating that the statistical associations might have occurred by chance. Conclusion: MSR provides a tool to search for risk-related SNP combinations of common traits or diseases. However, the search process does not always find meaningful SNP combinations in a dataset.
BMC Medical Genetics, 2009
Background: The aim of this study was to examine the associations between 16 specific single nucleotide polymorphisms (SNPs) in 8 obesity-related genes and overall and cause-specific mortality. We also examined the associations between the SNPs and body mass index (BMI) and change in BMI over time. Methods: Data were analyzed from 9,919 individuals who participated in two large community-based cohort studies conducted in Washington County, Maryland in 1974 (CLUE I) and 1989 (CLUE II). DNA from blood collected in 1989 was genotyped for 16 SNPs in 8 obesity-related genes: monoamine oxidase A (MAOA), lipoprotein lipase (LPL), paraoxonase 1 and 2 (PON1 and PON2), leptin receptor (LEPR), tumor necrosis factor-α (TNFα), and peroxisome proliferative activated receptor-γ and-δ (PPARG and PPARD). Data on height and weight in 1989 (CLUE II baseline) and at age 21 were collected from participants at the time of blood collection. All participants were followed from 1989 to the date of death or the end of follow-up in 2005. Cox proportional hazards regression was used to obtain the relative risk (RR) estimates and 95% confidence intervals (CI) for each SNP and mortality outcomes. Results: The results showed no patterns of association for the selected SNPs and the all-cause and cause-specific mortality outcomes, although statistically significant associations (p < 0.05) were observed between PPARG rs4684847 and all-cause mortality (CC:
BioImpacts, 2017
Introduction: Obesity is commonly linked up with several life-threatening diseases. This study aims to investigate the association of fatty acid synthase (FASN) rs4246445, rs2229425, rs2228305, and rs2229422 single nucleotide polymorphisms (SNPs) with the risk of overweight and obesity in the Malaysian population. Methods: Blood samples were collected from 1030 individuals who were grouped into normal, overweight, and obese categories. Blood biochemistry test and lipid profiling were performed and genomic DNA was extracted. Genotyping was performed using hydrolysis probes and odd ratio with 95% CI was calculated for risk association analysis. Linkage disequilibrium and haplotypes analyses were carried out using SHEsis software. Results: We found that the hemoglobin and white blood cell counts were significantly high in the obese subjects. There is a lack of evidence to link the FASN SNPs with the risk of overweight and obesity in the population. All 4 SNPs were seemed to be in linkage equilibrium. Five common haplotypes were identified in this study but none of them was significantly associated with overweight and obesity in the population. Conclusion: Our findings suggest a lack of evidence to associate the FASN rs4246445, rs2229425, rs2228305, and rs2229422 SNPs with the risk of overweight and obesity in the Malaysian population. All 4 SNPs were independent of each other and not all identified haplotypes were significantly associated with overweight and obesity in this study.
International journal of obesity (2005), 2018
Obesity is an important risk factor for the development of diseases such as diabetes mellitus, hypertension, and dyslipidemia; however, a small number of individuals with long-standing obesity do not present with these cardiometabolic diseases. Such individuals are referred to as metabolically healthy obese (MHO) and potentially represent a subgroup of the general population with a protective genetic predisposition to obesity-related diseases. We hypothesized that individuals who were metabolically healthy, but significantly obese (BMI ≥ 35 kg/m) would represent a highly homogenous subgroup, with which to investigate potential genetic associations to obesity. We further hypothesized that such a cohort may lend itself well to investigate potential genotypes that are protective with respect to the development of cardiometabolic disease. In the present study, we implemented this novel selection strategy by screening 892 individuals diagnosed as Class 2 or Class 3 obese and identified 3...
Nutricion hospitalaria
obesity affects more than a third of Mexican population. Oxidative stress participates actively in the etiology of this phenomenon. Glutathione peroxidase-1 (GPX-1) plays a protective role against oxidative stress. The SNP Pro200Leu (rs10504050) has been reported to affect the activity of the enzyme. to determine the frequency of rs10504050 polymorphism in women with obesity and normal weight control, asses the concentration of peripheral TBARS and evaluate the consumption of pro and antioxidants. 104 women with obesity and 70 healthy controls (CG) were included in the study. Anthropometric, biochemical, clinical and dietary features were evaluated. GPx-1 rs10504050 was determined by PCR/RFLP method. TBARS was assayed spectrophotometrically in plasma. The subjects were stratified and compared by obesity grades and by subgroups of prediabetes and diabetes condition. Statistical analysis included ANOVA of Kruskal Wallis, Xi squared and Pearson correlation. for rs10504050 polymorphism ...
International Journal of General Medicine
Background: Obesity is a major health threat worldwide. It predisposes individuals to diabetes, cardiovascular complications, and cancer. Genetic and environmental factors are responsible for the increasing incidence of obesity. In this study, we investigated the genetic factors associated with obesity in young Saudi women. Subjects and Methods: In this cross-sectional study, 131 young Saudi female students were recruited. Body mass index (BMI), waist-hip ratio, blood glucose, triglyceride, cholesterol, HDL, LDL, and vitamin D3 levels of the subjects were determined. Twelve SNPs of different genes that showed a correlation with obesity in different population were tested, namely GNPDA2 (rs10938397), TCF7L2 (rs10885409), FTO (rs1477196), ADIPOQ (rs1501299), MC4R (rs17782313), ABCA1 (rs1800977), FTO (rs1861868), VDR (rs2228570), VDR (rs731236), VDR (rs7975232), ADIPOQ (rs266729), and PFPK (rs6602024). Student's t-test was conducted for all parameters. Pearson correlation was performed to identify the correlated variables. The frequencies of different risk alleles were determined by direct counting of the test allele divided by the total number of alleles and compared. Results: Only two SNPs, rs1861868 of FTO and rs7975232 of VDR, of the twelve tested SNPs showed significant protective associations with the BMI with odds ratio 0.3886 (0.1761-0.8572); p 0.0192 and odds ratio 0.4563 (0.2343-0.8888); p 0.0211, respectively. Conclusion: The current study showed that minor alleles, "T" of FTO and "A" of VDR, might be protective factors against increased BMI in young Saudi female subjects. To elucidate this association, further studies with larger sample size involving both sexes are required.