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Association study between DNA methylation and genetic variation of APOE gene with the risk of coronary artery disease.

ABSTRACT: Coronary artery disease (CAD) is a common health problem with a high rate of disability and death. Dyslipidemia and altered metabolism of Apo-lipoproteins are involved in the CAD pathogenesis. The current study investigated two common polymorphisms (rs429358 and rs7412) and promoter DNA methylation status of APOE in the Iranian CAD patients and control subjects. Two hundred angiographically documented CAD patients and 200 control subjects were included in the study. The APOE polymorphism analysis was done by PCR-RFLP technique and DNA methylation status was evaluated by methylation specific PCR. The assay of lipid levels was conducted using standard colorimetric protocols. Results indicated that the frequency of ?3/?4 and ?2/?3 genotypes was significantly more common in CAD group compared with control group. Relative to wild type genotype (?3/?3), CAD patients with ?3/?4 and ?2/?3 genotypes displayed significantly higher concentration of total-cholesterol and LDL-cholesterol. The frequency of DNA methylation of APOE was similar between the two studied groups. However, the methylation frequency of APOE gene was significantly higher in triple stenotic vessels relative to single stenotic vessels (P=0.032). In conclusion The present study indicated that the rs429358 and rs7412 polymorphisms are significantly risk factors for development and severity of CAD. Also, APOE methylation status may be involved in the severity but not in the development of CAD.

SUBMITTER: Ghaznavi H

PROVIDER: S-EPMC6363939 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Association study between DNA methylation and genetic variation of APOE gene with the risk of coronary artery disease.

Ghaznavi Habib H Kiani Ali Asghar AA Soltanpour Mohammad Soleiman MS

Molecular biology research communications 20181201 4

Coronary artery disease (CAD) is a common health problem with a high rate of disability and death. Dyslipidemia and altered metabolism of Apo-lipoproteins are involved in the CAD pathogenesis. The current study investigated two common polymorphisms (rs429358 and rs7412) and promoter DNA methylation status of APOE in the Iranian CAD patients and control subjects. Two hundred angiographically documented CAD patients and 200 control subjects were included in the study. The APOE polymo ...[more]

PMID: 30788380

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Project description:Large-scale genome-wide association studies have identified hundreds of single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD). However, collectively, these explain <20% of the heritability. Hypothesis: Here, we hypothesize that mitochondrial (MT)-SNVs might present one potential source of this “missing heritability”. Methods: We analyzed 265 MT-SNVs in ~500,000 UK Biobank individuals, exploring two different CAD definitions: a more stringent (myocardial infarction and/or revascularization; HARD = 20,405), and a more inclusive (angina and chronic ischemic heart disease; SOFT = 34,782). Results: In HARD cases, the most significant (p < 0.05) associations were for m.295C>T (control region) and m.12612A>G (ND5), found more frequently in cases (OR = 1.05), potentially related to reduced cardiorespiratory fitness in response to exercise, as well as for m.12372G>A (ND5) and m.11467A>G (ND4), present more frequently in controls (OR = 0.97), previously associated with lower ROS production rate. In SOFT cases, four MT-SNVs survived multiple testing corrections (at FDR < 5%), all potentially conferring increased CAD risk. Of those, m.11251A>G (ND4) and m.15452C>A (CYB) have previously shown significant associations with body height. In line with this, we observed that CAD cases were slightly less physically active, and their average body height was ~2.00 cm lower compared to controls; both traits are known to be related to increased CAD risk. Gene-based tests identified CO2 associated with HARD/SOFT CAD, whereas ND3 and CYB associated with SOFT cases (p < 0.05), dysfunction of which has been related to MT oxidative stress, obesity/T2D (CO2), BMI (ND3), and angina/exercise intolerance (CYB). Finally, we observed that macro-haplogroup I was significantly (p < 0.05) more frequent in HARD cases vs. controls (3.35% vs. 3.08%), potentially associated with response to exercise. Conclusions: We found only spurious associations between MT genome variation and HARD/SOFT CAD and conclude that more MT-SNV data in even larger study cohorts may be needed to conclusively determine the role of MT DNA in CAD.

Dataset Information

Association study between DNA methylation and genetic variation of APOE gene with the risk of coronary artery disease.

Publications

Association study between DNA methylation and genetic variation of <i>APOE</i> gene with the risk of coronary artery disease.

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