Association of (rs429358 and rs7412) and (Q192R and L55M) Variants with Myocardial Infarction in the Pashtun Ethnic Population of Khyber Pakhtunkhwa, Pakistan.

Coronary Artery Diseases (CAD) remains the top among Non-communicable Diseases (NCDs). Variations in () and () have been associated with Myocardial Infarction (MI) in several populations. However, despite the high prevalence of CAD, no such study has been reported in the Pashtun ethnic population of Pakistan. We have conducted a two-stage (i.e., screening and validation) case-control study in which 200 cases and 100 control subjects have been recruited. In the first stage, Whole Exome Sequencing (WES) was used to screen for pathogenic variants of Myocardial Infarction (MI). In the second stage, selected variants of both and genes (rs7412, rs429358, rs854560, and rs662) were analyzed through MassARRAY genotyping. Risk Allele Frequencies (RAFs) distribution and association of the selected SNPs with MI were determined using the Chi-square test and logistic regression analysis. WES identified a total of 12 sequence variants in and 16 in Genotyping results revealed that variant rs429358 (ɛ4 allele and ɛ3/ɛ4 genotype) showed significant association in MI patients (OR = 2.11, value = 0.03; 95% CI = 1.25-2.43); whereas no significant difference (˃ 0.05) was observed for rs7412. Similarly, the R allele of Q192R (rs662) was significantly associated with cases (OR = 1.353, value = 0.048; 95% CI = 0.959-1.91), with particular mention of RR genotype (OR = 1.523, value = 0.006; 95% CI = 1.087-2.132). Multiple logistic regression analysis showed that rs429358 (C allele) and rs662 (R allele) have a significantly higher risk of MI after adjustment for the conventional risk factors. Our study findings suggested that the rs429358 variant of APOE and PON1 Q192R are associated with MI susceptibility in the Pashtun ethnic population of Pakistan.