Additive and Interactive Associations of Environmental and Sociodemographic Factors with the Genotypes of Three Glutathione S-Transferase Genes in Relation to the Blood Arsenic Concentrations of Children in Jamaica

Arsenic (As) is a metalloid that has been classified as a xenobiotic with toxic effects on human beings, especially on children. Since the soil in Jamaica contains As, dietary intake is considered the main source of As exposure in Jamaicans. In addition, glutathione S-transferase (GST) genes, including GSTT1, GSTP1, and GSTM1, play an important role in the metabolism of xenobiotics including As in humans. Using data from 375 typically developing children (2–8 years) in Jamaica, we investigated the environmental and sociodemographic factors, as well as their possible interactions with the children’s genotype for GST genes in relation to having a detectable level of blood As concentration (i.e., >1.3 μg/L). Using multivariable logistic regression, we have identified environmental factors significantly associated with blood As concentrations that include a child’s age, parental education levels, and the consumption of saltwater fish, cabbage, broad beans, and avocado (all p < 0.01). Based on the multivariable analysis including gene x environment interactions, we found that among children with the Ile/Ile genotype for GSTP1 Ile105Val, children who consumed avocado had higher odds of having a detectable blood As concentration compared to children who did not eat avocado.

Association of GSTP1 Ile105Val polymorphism with the risk of coronary heart disease: An updated meta-analysis

Background Numerous case-control studies have investigated the association between GSTP1 Ile105Val polymorphism and CHD risk, but the results from published studies were inconclusive. The present meta-analysis was performed to derive a more precise estimation. Methods PubMed, EMBASE, and Web of Science database searches were conducted to retrieve relevant articles. Results Ultimately, 5,451 CHD cases and 5,561 controls from 15 studies were included. Pooled analysis did not yield any statistically significant association between GSTP1 Ile105Val polymorphism and CHD risk for the overall population (Val vs. Ile: OR, 1.05; 95% CI, 0.93 to 1.18; Val/Val vs. Ile/Ile: OR, 1.09; 95% CI, 0.83 to 1.42; Val/Ile vs. Ile/Ile: OR, 1.09; 95% CI, 0.93 to 1.28; Val/Val vs. Val/Ile+Ile/Ile: OR, 1.04; 95% CI, 0.83 to 1.30; Val/Val+Val/Ile vs. Ile/Ile: OR, 1.14; 95% CI, 0.97 to 1.33). Subgroup analyses and sensitivity analyses indicated that GSTP1 Ile105Val polymorphism was still not associated with an increased risk of CHD. After excluding studies detected by Galbraith plots as major sources of heterogeneity, these relationships were still not significant. Conclusions The overall results did not reveal a major role of the GSTP1 Ile105Val polymorphism in modulating CHD risk. Well-designed studies with large sample sizes are needed to validate our findings and explore the possible gene-gene or gene-environment interactions.

The Association of Antioxidants Gene Polymorphisms (SOD2 Ala16Val, GPx1 Pro198Leu, GSTP1 Ile105Val, and Cat −21 A/T) and Risk of Type 2 Diabetes Mellitus

BACKGROUND: Antioxidant gene polymorphism is one of the genetic risk factors associated with type 2 diabetes mellitus (T2DM) incidence. AIM: This study was to analyze the association of superoxide dismutase 2 (SOD2) Ala16VAl, glutathione peroxidase (GPx1) Pro198Leu, glutathione S-transferase Pi1 (GSTP1) Ile105Val, and Cat −21 A/T gene polymorphisms and risk of T2DM. METHODS: We genotyped deoxyribonucleic acid of 120 T2DM patients and 80 healthy control by polymerase chain reaction and restriction fragment length polymorphism method, using a specific restriction enzyme. RESULTS: This study showed that the Val/Val of SOD2 was significantly associated with an increased risk of T2DM compared to the Ala/Ala+Ala/Val (p = 0.011; odds ratio [OR] = 2.220; confidence interval [CI] = 1.234–3.992). The TT genotype of Cat gene was also significantly associated with an increased risk of T2DM compared to the AA genotype (p = 0.027; OR = 5.000; CI = 1.079–23.176) and TT genotype to the AA+AT genotype (p = 0,030; OR = 4.738; CI = 1.039–21.600). However, there was no difference in all genetic models of GPx1 Pro198Leu and GSTP1 Ile105Val gene polymorphisms (p > 0.05). CONCLUSION: This study indicates that the Val/Val under the recessive model of SOD2 gene also TT genotype under the co-dominant model of Cat gene and TT genotype under the recessive model of Cat gene were associated with risk factors for T2DM occurrence.

Glutathione S-transferase gene polymorphisms and risk of nasal or colorectal polyposis

We observed inconsistent conclusions regarding the genetic role of glutathione S-transferase gene polymorphisms, including glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase pi (GSTP1) Ile105Val polymorphisms, in the susceptibility to nasal or colorectal polyposis (NP or CP). Thus, we aimed to perform a meta-analysis to comprehensively evaluate this association by applying Stata/SE software. After the heterogeneity assumption, Mantel–Haenszel statistics were used to obtain the odds ratio (OR), 95% confidence interval (95% CI) and P-value of the association test (PA). We obtained a total of 235 articles by searching online databases. After screening, ten eligible case–control studies were finally enrolled in our meta-analysis. For the meta-analysis of the GSTT1 gene under present versus null, we observed a decreased risk of NP [OR = 0.65; PA=0.018], but not CP. In addition, we did not detect any evident association between the GSTM1 present/null polymorphism and NP or CP risk. For the meta-analysis of the GSTP1 Ile105Val polymorphism, compared with controls, an increased risk of NP cases was detected under the models of Val versus Ile (OR = 1.36; PA=0.027), Ile/Val versus Ile/Ile (OR = 1.70; PA=0.011) and Ile/Val+Val/Val versus Ile/Ile (OR = 1.65; PA=0.010). In conclusion, the null genotype of the GSTT1 polymorphism may be linked to an increased susceptibility to NP, whereas the Ile/Val genotype of the GSTP1 Ile105Val polymorphism may be associated with a decreased risk of NP.