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ABSTRACT Apolipoprotein E (APOE) gene have two common polymorphic risk alleles APOE112 and APO158 which constitute six isoforms categorized in three genotypes E2 ([straight epsilon]2[straight epsilon]2, [straight epsilon]2[straight epsilon]3, [straight epsilon]2[straight epsilon]4), E3 ([straight epsilon]3[straight epsilon]3) and E4 ([straight epsilon]3[straight epsilon]4, [straight epsilon]4[straight epsilon]4). We aimed to assess APOE genotypes association with myocardial infarction in Pakistani cohort. Serum lipid levels were determined of survivors of myocardial infarction (n=100) and control (n=100) and genotyped using high throughput fluorescence based TaqMan and KASPar assays. The APOE158 risk allele frequency was significantly lower in diseased (p-value 0.025). Three alleles E2 (15%), E3 (71%), E4 (14%) and E2 (5%), E3 (76%), E4 (18%) were observed among control and MI patients respectively. The E2 genotype found significantly lower for total cholesterol compared to E3 (p-value=0.013) and E4 (p-value=0.006). LDL-cholesterol values of E2 genotypes were also significantly lower to E3 (p-value=0.002), E4 (p-value=0.009) and triglycerides levels (p-value=0.039) to E4.
The isoform [straight epsilon]3[straight epsilon]3 is more common among Pakistani population and genotype E2 can be considered as lipid lowering and protective. These findings conclude that APOE isoforms have genetic contribution with lipid levels and cardiovascular disease in Pakistan patients.
Key words Apolipoprotein E, risk allele, isoforms, high-throughput assay.
INTRODUCTION Coronary artery disease (CAD) and its complication, myocardial infarction (MI) is the more common cause of death in the world. A number of risk factors have been identified associated with coronary artery disease such as plasma concentration of lipids, inflammation markers, blood pressure, diabetes and smoking. These risk factors are consistent across the race and regions (Berry et al., 2012). MI is presented clinically due to atherosclerosis plaque development (Zdravkovic et al., 2004) and atherosclerosis is major cause of MI in Pakistan (Mushtaq et al., 2006, Wilson et al., 1998). Atherosclerosis is a chronic inflammatory and fibroproliferative disease mainly affecting the coronary arteries (Falk, 1999). Atherosclerosis development largely depends on plasma lipid concentrations and inflammatory response of the vascular tissues, in which cholesterol starts to deposit in peripheral tissues and accelerate the atherogenesis leading to premature cardiovascular events (Alonso et al., 2009).
Atherosclerotic lesions block the coronary passage which ultimately leads to heart, brain or extremities ischemia resulting in infarction to ischemia of the heart, brain or extremities, resulting in infarction.
Apolipoprotein-E...