APOEGene Polymorphism and Risk of Coronary Stenosis in Pakistani Population

Abstract

Genetic variation in lipid regulatory genes, particularly APOE, significantly influences the risk of coronary artery disease (CAD). This study aimed to assess the association between APOE polymorphism and angiographically assessed coronary stenosis in Pakistani population. A total of 695 subjects (22.3% female, mean age = 54 ± 11 years) presenting with chest pain were enrolled after obtaining written informed consent. CAD stenosis/extent was assessed by angiography. Patients were classified as having severe stenosis (≥70%), moderate stenosis (30–69%), and mild stenosis (<30%). CAD patients with ≥70% stenosis (n = 491) were further categorized based on possessing one, two, or three vessel diseases to assess the disease extent. Genomic DNA from leukocytes was isolated with DNA purification kit (Qiagen) and APOE polymorphisms (E2/E3/E4) were determined using TaqMan assays. Six hundred and seventy-two of 695 subjects were successfully genotyped. The frequency of APOE∗4 carriers (3/4 and 4/4 genotypes) was significantly higher in severe stenosis group (≥70%) as compared to mild group (<30%) (22.8% versus 13.01%; P = 0.01). In multiple regression, the odds ratio for APOE∗4 carriers to develop ≥70% stenosis was 2.16 (95% CI: 1.29–3.79; P < 0.005). In conclusion, the presence of APOE∗4 allele is a significant risk factor to develop severe coronary stenosis (>70%) among Pakistanis.

Association Study of Coronary Artery Disease-Associated Genome-Wide Significant SNPs with Coronary Stenosis in Pakistani Population

“…Only a small number of cases with mild/minimal coronary stenosis were available for comparison with severe coronary stenosis. Despite this limitation, we have previously reported a significant association of APOE with coronary stenosis in our sample [ 38 ] which has been confirmed by another study that also used an angiography-assessed small sample [ 36 ]. Recently, more than 160 loci have been implicated with CAD [ 4 , 39 ].…”

“…While one study examined 13 CAD risk SNPs in relation to premature CAD (mean age = ~40) assessed by angiography in a total sample of 650 [ 36 ], the other study screened 6 SNPs in 624 subjects where CAD cases were assessed only clinically (no angiography) and controls were apparently healthy subjects [ 37 ]. While no significant association was observed in the latter case-control study, 5 nominal significant associations were seen in the angiography-assessed premature CAD, including APOE , which we have also previously reported in our angiography-assessed sample [ 38 ]. Of the other 4 significant SNPs reported by Ansari et al [ 36 ], only one SNP ( MIA3 /rs17465367) overlapped with our SNPs and those of Shahid et al [ 37 ], which was not significant in both studies.…”

Risk of progression from subjective cognitive decline to mild cognitive impairment: The role of study setting

“…APOE genotyping was completed by the same laboratory for both the PITT-ADRC and MYHAT study participants using TaqMan SNP genotyping assays, as described previously [28].…”

Apolipoprotein E Gene Variants and Risk of Coronary Heart Disease: A Meta-Analysis

“…Another meta-analysis including 14 studies showed that subjects with ε 4 allele were associated with 26% increased risk of CHD compared with ε 3 allele [13]. Since the publication of these two meta-analyses, numerous studies have appeared in recent years [14–17]. However, differences in study design, end point validation, choice of subjects, and limited statistical power have led to different results of Apo E genotypes on CHD risk in the general population.…”