<p>Association of <em>GSTP1</em>, <em>GSTT1</em> and <em>GSTM1</em> Gene Variants with Coronary Artery Disease in Iranian Population: A Case–Control Study</p>

Abstract

Background: Coronary artery disease (CAD) is a multifactorial disease that may be caused by the interaction between environmental and genetic risk factors. Glutathione S-transferases (GSTs) are known to participate in detoxification and metabolism of a wide range of xenobiotic compounds and oxidative stress products. Considering the interaction between environmental and genetic factors in CAD, we investigated the genetic polymorphisms of GSTM1, GSTT1, and GSTP1 in the Iranian population. Patients and Methods: Two hundred and forty-four CAD cases and 281 healthy controls were studied. The genotype of GSTM1, GSTT1, and GSTP1 genes was determined by multiplex polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques. Multivariable logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CI). Multifactor dimensionality reduction (MDR) analysis was also carried out to analyze the gene-gene and gene-environment interaction.Results: The genotype and allele distribution of the three variations were not significantly different between CAD patients and controls (p > 0.05). The subgroup analysis revealed no significant gene-gene interactions or gene-gene combination effects linked to CAD susceptibility. However, MDR analysis selected the GSTM, GSTT pairwise and three genes combination models associated with the susceptibility to CAD. In addition, its result revealed that smoking in combination with GSTM1 (two-way) and GSTT, GSTP (three-way) genes might increase the risk of CAD. Furthermore, a significant interaction between GSTT1-null polymorphism and dyslipidemia was found in multivariable logistic regression analyses in the gene-environmental interactions on CAD risk. Conclusion: Our results suggest that the GSTM1, GSTT1 and GSTP1 genetic variations are not directly associated with the susceptibility to CAD in Iranian patients. Due to MDR results, there might be a non-linear association between interactions of two or three genes and smoking with CAD. There is also an association between CAD risk factors and GST variations, which requires supplementary confirmation with larger sample sizes.

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

“…The present study included 5,451 CHD cases and 5,561 controls in 15 studies, which could provide more sufficient statistical power. Compared with previous studies, more than four relevant studies [4, 19,22,23] were involved in present meta-analysis but not in theirs. The sample size of two previous studies was relatively small and data was not sufficient for subgroup analysis.…”

“…A number of case-control studies [4,7,8,[12][13][14][15][16][17][18][19][20][21][22][23] have investigated the relationship between GSTP1 Ile105Val polymorphism with the risk of CHD, with equivocal conclusions. Recently, one meta-analysis [24] revealed that a significant association exists between GSTP1 null genotype and CHD, and the other one [25] suggested that GSTP1 null genotype could impact individual susceptibility to atherosclerotic cardiovascular diseases.…”

“…Recently, one meta-analysis [24] revealed that a significant association exists between GSTP1 null genotype and CHD, and the other one [25] suggested that GSTP1 null genotype could impact individual susceptibility to atherosclerotic cardiovascular diseases. However, numerous relevant publications [4, 19,22,23] did not appear in their meta-analyses. Moreover, their meta-analyses did not evaluate the strength of the association between GSTP1 Ile105Val polymorphism and CHD risk in the specific genetic models, dominant model, homozygote model, heterozygote model, recessive model, and an allele comparison, respectively.…”

Genetic Association of rs10757278 on Chromosome 9p21 and Coronary Artery Disease in a Saudi Population

“…Certain risk factors for CAD are modifiable, such as lifestyle changes and medication management. 3 However, there are numerous genetic and environmental risk factors contributing to CAD with high mortality and morbidity rate in most developed and developing countries. 4 Myocardial infarction and angina are considered coronary vascular diseases (CVD), reported in 31% of the population worldwide.…”

Influence of GSTP1 Polymorphism on the Clinical Outcomes of Patients With Advanced NSCLC Receiving First-Line Bevacizumab-Based Regimen: A Real-World Retrospective Study

“…12 Previous study demonstrated that GSTP1 gene played an important role in biodetoxification or biotransformation by binding to reduced glutathione. 13 As one of the phase-Ⅱ metabolizing enzymes, GSTP1 was reported to catalyze detoxifying endogenous reactions with GSH and protect cellular macromolecules from damage caused by a wide variety of endogenous and exogenous molecules, including chemotherapeutic agents. 14 Therefore, GSTP1 were crucial for the cell defense system.…”