Dataset Information

The Association between Serum LDL Cholesterol and Genetic Variation in Chromosomal Locus 1p13.3 among Coronary Artery Disease Patients.

ABSTRACT:

Background

Several polymorphisms of a locus on chromosome 1p13.3 have a significant effect on low-density lipoprotein cholesterol (LDL-C), atherosclerosis, and acute coronary syndrome (ACS).

Methods

We aimed to investigate the association between rs599839, rs646776, and rs4970834 of locus 1p13.3 and serum LDL-C and severity of coronary artery stenosis in ACS patients. Genotyping of the rs599839, rs646776, and rs4970834 polymorphisms was performed on Arab patients undergoing coronary angiography for ACS. Patients were divided into group A (ACS with insignificant stenosis (<50%)) and group B (with significant stenosis (≥ 50%)).

Results

Patients carrying the minor G allele in rs599839 had significantly lower mean of LDL-C (2.58 versus 3.44 mM, P = 0.026) than homozygous A allele carriers (GG versus AA). Carriers of minor C allele in rs64776 had significantly higher mean of HDL-C (2.16 versus 1.36 mM, P = 0.004) than carriers of the T alleles (AA versus GG). The odd ratio and 95% confidence interval for dominant model for G allele carriers of rs599839 were 0.51 (0.30-0.92), P = 0.038, among patients with significant stenosis.

Conclusions

Polymorphisms rs646776 and rs599839 of locus 1p13.3 were significantly associated with LDL-C and other lipid parameters. In addition, the G-allele carriers of variant rs599839 had a significant protective effect against the atherosclerosis.

SUBMITTER: Rizk NM

PROVIDER: S-EPMC4370099 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Association between Serum LDL Cholesterol and Genetic Variation in Chromosomal Locus 1p13.3 among Coronary Artery Disease Patients.

Rizk Nasser M NM El-Menyar Ayman A Egue Huda H Souleman Wais Idil I Mohamed Baluli Hissa H Alali Khalid K Farag Fathi F Younes Noura N Al Suwaidi Jassim J

BioMed research international 20150308

<h4>Background</h4>Several polymorphisms of a locus on chromosome 1p13.3 have a significant effect on low-density lipoprotein cholesterol (LDL-C), atherosclerosis, and acute coronary syndrome (ACS).<h4>Methods</h4>We aimed to investigate the association between rs599839, rs646776, and rs4970834 of locus 1p13.3 and serum LDL-C and severity of coronary artery stenosis in ACS patients. Genotyping of the rs599839, rs646776, and rs4970834 polymorphisms was performed on Arab patients undergoing corona ...[more]

PMID: 25969834

Similar Datasets

Project description:BackgroundThe role of cholesteryl ester transfer protein (CETP) in the metabolism of high-density lipoprotein cholesterol (HDL-C) is well studied but still controversial. More recently, genome-wide association studies and meta-analyses reported the association of a promoter variant (rs3764261) with HDL-C in Caucasians and other ethnic groups. In this study, we have examined the role of genetic variation in the promoter region of CETP with HDL-C, CETP activity, coronary artery disease (CAD), CAD risk factors, and the interaction of genetic factors with environment in a unique diabetic cohort of Asian Indian Sikhs.Methods and resultsWe genotyped four variants; three tagging single nucleotide polymorphisms from promoter (rs3764261, rs12447924, rs4783961) and one intronic variant (rs708272 Taq1B) on 2431 individuals from the Sikh Diabetes study. Two variants (rs3764261 and rs708272) exhibited a strong association with HDL-C in both normoglycemic controls (β=0.12; P=9.35×10 for rs3764261; β=0.10, P=0.002 for rs708272) and diabetic cases (β=0.07, P=0.016 for rs3764261; β=0.08, P=0.005 for rs708272) with increased levels among minor homozygous 'AA' carriers. In addition, the same 'A' allele carriers in rs3764261 showed a significant decrease in systolic blood pressure (β=-0.08, P=0.002) in normoglycemic controls. Haplotype analysis of rs3764261, rs12447924, rs4783961, and rs708272 further revealed a significant association of 'ATAA' haplotype with an increased HDL-C (β=2.71, P=6.38×10) and 'CTAG' haplotype with decreased HDL-C levels (β=-1.78, P=2.5×10). Although there was no direct association of CETP activity and CETP polymorphisms, low CETP activity was associated with an increased risk to CAD (age, BMI, and sex-adjusted odds ratio=2.2; 95% confidence interval: 1.4-3.4; P=0.001) in this study. Our data revealed a strong interaction of rs3764261 and rs708272 for affecting the association between CETP activity and HDL-C levels (P=2.2×10 and P=4.4×10, respectively).ConclusionOur results, in conjunction with earlier reports confirm low CETP activity to be associated with higher CAD risk. Although there was no direct association of CETP activity with CETP polymorphisms, our findings revealed a significant interaction between CETP variants and CETP activity for affecting HDL-C levels. These results urge a deeper evaluation of the individual genetic variation in the CETP before implementing pharmaceutical intervention of blocking CETP for preventing CAD events.

Project description:BackgroundGenome-wide association studies identified ADAMTS7 as a risk locus for coronary artery disease (CAD). Functional studies suggest that ADAMTS7 may promote cellular processes in atherosclerosis. We sought to examine the association between genetic variation at ADAMTS7 and measures of atherosclerosis using histological, angiographic, and clinical outcomes data.Methods and resultsThe lead CAD-associated single-nucleotide polymorphism rs3825807 at the ADAMTS7 locus was genotyped. The G allele (reduced ADAMTS7 function) was associated with a smaller fibrous cap (P=0.017) and a smaller percentage area of α-actin (smooth muscle cell marker) in the intima (P=0.017), but was not associated with calcification or plaque thickness, following ex vivo immunohistochemistry analysis of human coronary plaques (n=50; mean age 72.2±11.3). In two independent cohorts (Southampton Atherosclerosis Study [n=1359; mean age 62.5±10.3; 70.1% men] and the Emory Cardiovascular Biobank [EmCAB; n=2684; mean age 63.8±11.3; 68.7% men]), the G allele was associated with 16% to 19% lower odds of obstructive CAD (Southampton Atherosclerosis Study: odds ratio, 0.81; 95% confidence interval, 0.67-0.98; EmCAB: odds ratio, 0.84; 95% confidence interval, 0.75-0.95) with similar effects for multivessel, left anterior descending, and proximal CAD. Furthermore, each copy of the G allele was associated with lower angiographic severity Gensini score (Southampton Atherosclerosis Study, P=0.026; EmCAB, P<0.001), lower Sullivan Extent score (Southampton Atherosclerosis Study, P=0.029; EmCAB, P<0.001), and a 23% lower risk of incident revascularization procedures (EmCAB: hazard ratio, 0.76; 95% confidence interval, 0.59-0.98). There were no associations with all-cause mortality or incident myocardial infarction.ConclusionsGenetic variation at the ADAMTS7 locus is associated with several complementary CAD phenotypes, supporting the emerging role of ADAMTS7 in atherosclerosis and may represent a potential drug target.

Dataset Information

The Association between Serum LDL Cholesterol and Genetic Variation in Chromosomal Locus 1p13.3 among Coronary Artery Disease Patients.

Background

Methods

Results

Conclusions

Publications

The Association between Serum LDL Cholesterol and Genetic Variation in Chromosomal Locus 1p13.3 among Coronary Artery Disease Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets