Temel Şehime Gülsün, Ergören Mahmut Çerkez
Departments of Medical Genetics, and Histology&Embryology, Faculty of Medicine, Uludað University; Bursa-Turkey.
Anatol J Cardiol. 2019 Jan;21(1):31-38. doi: 10.14744/AnatolJCardiol.2018.90907.
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.
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.
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.
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.
近期全基因组关联研究已证实，9号染色体p21.3位点的CDKN2B-AS1基因内多态性增加了患冠状动脉疾病（CAD）或心肌梗死的易感性。CDKN2B-AS1的常见变体（包括rs4977574 A>G和rs1333040 C>T）在全球许多人群中被确定与CAD直接相关，并被认为是CAD早期检测的生物标志物。在土族塞人人群中，缺乏对CDKN2B-AS1 rs4977574 A>G和rs1333040 C>T基因修饰与CAD之间关联的研究。本研究的目的是调查这些变体对土族塞人人群患CAD易感性的潜在影响及其对脂质代谢的作用。
将71例经血管造影确诊为CAD的患者纳入CAD组，将153例无CAD症状的自愿受试者纳入对照组。通过聚合酶链反应进行CDKN2B-AS1基因多态性的基因分型，随后进行限制性片段长度多态性分析。
未观察到rs4977574和rs1333040单核苷酸多态性与两个研究组之间存在统计学显著关联[比值比（OR）：0.763，p = 0.185，95%置信区间（CI）：0.511 - 1.139；以及OR：1.060，p = 0.802，95% CI：0.672 - 1.671]。然而，发现rs2977574 G和rs1333040 T等位基因（风险等位基因）与CAD组中较高的血清总胆固醇水平和较低的高密度脂蛋白胆固醇水平相关（分别为p = 0.019，p = 0.006和p = 0.022，p = 0.031）。据我们所知，这是第一项确定rs1333040对脂质代谢影响的研究。
rs4977574 G和rs1333040 T等位基因的存在以及相互作用可能作为与脂质代谢相关的环境因素而存在，并可能是土族塞人人群中CAD发生的原因。
