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Anatol J Cardiol. 2019 Jan;21(1):31-38. doi: 10.14744/AnatolJCardiol.2018.90907.

The association between the chromosome 9p21 CDKN2B-AS1 gene variants and the lipid metabolism: A pre-diagnostic biomarker for coronary artery disease.

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1
Departments of Medical Genetics, and Histology&Embryology, Faculty of Medicine, Uludað University; Bursa-Turkey. sehime@uludag.edu.tr.

Abstract

OBJECTIVE:

Recent genome-wide association studies have established that polymorphisms within CDKN2B-AS1 of chr9p21.3 locus increased susceptibility to coronary artery disease (CAD) or myocardial infarction. Common variants of CDKN2B-AS1 (including rs4977574 A>G and rs1333040 C>T) are determined to be directly associated with CADs in many populations worldwide and suggested biomarkers for the early detection of CAD. There is a lack of investigation for the association between CDKN2B-AS1 rs4977574 A>G and rs1333040 C>T genetic modifiers and CAD in a Turkish Cypriot population. The aim of the present study was to investigate the potential effects of these variants on susceptibility to developing CAD in a Turkish Cypriot population and their contribution to lipid metabolism.

METHODS:

Seventy-one patients with angiography-confirmed CAD were recruited to the CAD group, whereas 153 voluntary subjects without CAD symptoms were enrolled to the control group. Genotyping for the CDKN2B-AS1 gene polymorphisms was performed by polymerase chain reaction, followed by restriction fragment length polymorphism analysis.

RESULTS:

There is no statistical significant association observed between rs4977574 and rs1333040 single-nucleotide polymorphisms and two studied groups [odds ratio (OR): 0.763, p=0.185, 95% confidence interval (CI): 0.511-1.139 and OR: 1.060, p=0.802, 95% CI: 0.672-1.671, respectively]. However, rs2977574 G and rs1333040 T alleles-the risk alleles-were found to be associated with higher level of serum total cholesterol and lower level of high-density lipoprotein-cholesterol in the CAD group (p=0.019, p=0.006 and p=0.022, p=0.031, respectively). To our knowledge, this is the first study that establishes the effect of rs1333040 on lipid metabolism.

CONCLUSION:

The presence of rs4977574 G and rs1333040 T alleles and interaction may exist as environmental factors associated with lipid metabolism and might be responsible for the development of CAD in a Turkish Cypriot population.

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