Genetic Polymorphisms and Genetic Risk Scores Contribute to the Risk of Coronary Artery Disease (CAD) in a North Indian Population

Coronary artery disease (CAD) is the leading cause of death in India. Many genetic polymorphisms play a role in regulating oxidative stress, blood pressure and lipid metabolism, contributing to the pathophysiology of CAD. This study examined the association between ten polymorphisms and CAD in the Jat Sikh population from Northern India, also considering polygenic risk scores. This study included 177 CAD cases and 175 healthy controls. The genetic information of <i>GSTM1</i> (rs366631), <i>GSTT1</i> (rs17856199), <i>ACE</i> (rs4646994), <i>AGT</i> M235T (rs699), <i>AGT</i> T174M (rs4762), <i>AGTR1</i> A1166C (rs5186), <i>APOA5</i> (rs3135506), <i>APOC3</i> (rs5128), <i>APOE</i> (rs7412) and <i>APOE</i> (rs429358) and clinical information was collated. Statistical analyses were performed using SPSS version 27.0 and SNPstats. Significant independent associations were found for <i>GST*M1</i>, <i>GST*T1</i>, <i>ACE</i>, <i>AGT</i> M235T, <i>AGT</i> T174M, <i>AGTR1</i> A1166C and <i>APOA5</i> polymorphisms and CAD risk (all <i>p</i> < 0.05). The <i>AGT</i> CT haplotype was significantly associated with a higher CAD risk, even after controlling for covariates (adjusted OR = 3.93, 95% CI [2.39-6.48], <i>p</i> < 0.0001). The <i>APOA5/C3</i> CC haplotype was also significantly associated with CAD (adjusted OR = 1.86, 95% CI [1.14-3.03], <i>p</i> < 0.05). A higher polygenic risk score was associated with increased CAD risk (adjusted OR = 1.98, 95% CI [1.68-2.34], <i>p</i> < 0.001). Seven polymorphisms were independently associated with an increase in the risk of CAD in this North Indian population. A considerable risk association of <i>AGT</i>, <i>APOA5/C3</i> haplotypes and higher genetic risk scores is documented, which may have implications for clinical and public health applications.