Association of GSTPI, GSTTI and GSTMI Gene Variants with Coronary Artery Disease in Iranian Population: A Case-Control Study

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 GSTMI, GSTTI, and GSTPI in the Iranian population. Patients and Methods: Two hundred and forty-four CAD cases and 281 healthy controls were studied. The genotype of GSTMI, GSTTI, and GSTPI 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 GSTMI (two-way) and GSTT, GSTP (three-way) genes might increase the risk of CAD. Furthermore, a significant interaction between GSTTI -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 GSTMI, GSTTI and GSTPI 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. Keywords: GSTMI, GSTTI, GSTPI, detoxification system, polymorphisms, coronary artery disease