Abstract Coronary Artery Diseases (CAD) remains the top among Non-communicable Diseases (NCDs). Variations in Apolipoprotein E ( APOE ) and Paroxonase 1 ( PON1 ) 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 APOE and PON1 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 APOE and 16 in PON1. Genotyping results revealed that APOE variant rs429358 (ɛ4 allele and ɛ3/ɛ4 genotype) showed significant association in MI patients (OR = 2.11, p value = 0.03; 95% CI = 1.25–2.43); whereas no significant difference ( p ˃ 0.05) was observed for rs7412. Similarly, the R allele of PON1 Q192R (rs662) was significantly associated with cases (OR = 1.353, p value = 0.048; 95% CI = 0.959–1.91), with particular mention of RR genotype (OR = 1.523, p 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. Keywords: apolipoprotein E, rs7412, rs429358, polymorphism, single nucleotide polymorphism, coronary artery disease, cardiovascular disease, myocardial Infarction, Paroxonase 1 , Q192R, L55M, genetic biomarker, variant, whole exome sequencing, Pashtun population, Pakistan
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Naveed Rahman, Zakiullah, Asif Jan et al.. Association of APOE (rs429358 and rs7412) and PON1 (Q192R and L55M) Variants with Myocardial Infarction in the Pashtun Ethnic Population of Khyber Pakhtunkhwa, Pakistan. Genes. (2023). https://doi.org/10.3390/genes14030687 Naveed Rahman, Zakiullah, Asif Jan, Muhammad Saeed, Muhammad Asghar Khan, Zahida Parveen, Javaid Iqbal, Sajid Ali, Waheed Ali Shah, Rani Akbar, Fazli Khuda
1Department of Pharmacy, University of Peshawar, Peshawar 25000, [email protected] (A.J.); 2Department of Pharmacy, Qurtaba University of Science and Technology, Peshawar 25000, Pakistan 3Cardiology Unit Hayatabad Medical Complex, Peshawar 25000, Pakistan 4Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan 5Department of Environmental Sciences, University of Lakki Marwat KP, Marwat 28420, Pakistan 6Department of Biotechnology, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan 7Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan 