Association of GSTP1, GSTT1 and GSTM1 Gene Variants with Coronary Artery Disease in Iranian Population: A Case-Control Study

• Published in: International journal of general medicine 2020-01, Vol.13, p.249-259
• Main Authors: Pourkeramati, Alemeh, Zare Mehrjardi, Ehsan, Dehghan Tezerjani, Masoud, Seifati, Seyed Morteza
• Format: Article
• Language: English
• Subjects: coronary artery disease; detoxification system; gstm1; gstp1; gstt1; Original Research; polymorphism
• ISSN: 1178-7074; 1178-7074
• DOI: 10.2147/IJGM.S252552

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 , and in the Iranian population. Two hundred and forty-four CAD cases and 281 healthy controls were studied. The genotype of , and 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. 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 pairwise and three genes combination models associated with the susceptibility to CAD. In addition, its result revealed that smoking in combination with (two-way) and (three-way) genes might increase the risk of CAD. Furthermore, a significant interaction between -null polymorphism and dyslipidemia was found in multivariable logistic regression analyses in the gene-environmental interactions on CAD risk. Our results suggest that the and 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.