The T Allele of rs8075977 in the 5′-Flanking Region of the PEDF Gene Is Associated with Reduced Risk of Coronary Artery Disease in Elderly Chinese Men
The T Allele of rs8075977 in the 5′-Flanking Region of the PEDF Gene Is Associated with Reduced Risk of Coronary Artery Disease in Elderly Chinese Men
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PEDF 基因 5' 侧翼区域 rs8075977 的 T 等位基因与中国老年男性患冠状动脉疾病的风险降低相关。
DOI：
10.1620/tjem.241.297
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发表时间：
2017-04-01
影响因子：
2.2
通讯作者：
Zhu，Ping
中科院分区：
文献类型：
--
作者：
Ma，Shou-Yuan;Guo，Yuan-Yuan;Zhu，Ping
冠状动脉疾病(CAD)是一种具有遗传成分的多因素疾病。色素上皮衍生因子(PEDF)具有抗炎、抗氧化、抗血栓、抗血管生成等作用，作为动脉粥样硬化和冠心病的敏感标志物，受到越来越多的关注。为探讨PEDF单核苷酸多态(SNPs)与冠心病的关系，我们对416例老年汉族男性患者和528例无冠心病病史或心电图体征的老年男性患者进行病例对照研究。入选的冠心病患者(年龄≥，60岁)无生物亲缘关系。使用标签方法100%检测PEDF基因的常见变异(R2≥0.8，次要等位基因频率>；0.1)。使用描述人类DNA序列变异常见模式的HapMap Data-CHB和标签程序选择PEDF标签SNPs(TSNPs)。用连接酶检测反应(LDR)进行SNPs基因分型。选择了7个tSNP(rs8075977、rs11658342、rs1136287、rs12603825、rs12453107、rs6828和rs11078634)。其中，位于5‘-侧翼区的一个SNP rs8075977(C/T)对冠心病的易感性有显著影响。对照组T等位基因频率(52.7%)显著高于冠心病组(46.2%)(调整后OR=0.88，95%CI：0.80~0.96；P=0.005)。结论：PEDF基因5‘侧翼区rs8075977的T等位基因可能对冠心病具有保护作用。相反，该变异位点的C等位基因与中国汉族老年男性冠心病相关。
Coronary artery disease (CAD) is a multifactorial disease with a genetic component. Pigment epithelium-derived factor (PEDF) exerts anti-inflammatory, anti-oxidant, anti-thrombotic, and anti-angiogenic effects and thus has received increasing attention as a sensitive biomarker of atherosclerosis and CAD. To explore the potential association between PEDF single nucleotide polymorphisms (SNPs) and CAD, we performed this case-control study of consecutive elderly Chinese Han male patients (n = 416) and age-matched male controls (n = 528) without a history of CAD or electrocardiographic signs of CAD. The enrolled CAD patients (age ≥ 60 years) are not biologically related. A tag approach was used to examine 100% of common variations in the PEDF gene (r2 ≥ 0.8, minor allele frequency > 0.1). PEDF tag SNPs (tSNPs) were selected using the HapMap Data-CHB which describes the common patterns of human DNA sequence variation and Tagger program. SNPs were genotyped using ligase detection reaction (LDR). Seven tSNPs (rs8075977, rs11658342, rs1136287, rs12603825, rs12453107, rs6828 and rs11078634) were selected. Among them, only one SNP, rs8075977 (C/T) located in the 5'-flanking region, showed the significant effect on the susceptibility to CAD. The frequency of its T allele was significantly higher in the controls (52.7%) than that in the CAD group (46.2%) (adjusted OR = 0.88, 95% CI: 0.80-0.96; P = 0.005). In conclusion, the T allele of rs8075977 in the 5'-flanking region of the PEDF gene may be protective for CAD. Conversely, the C allele at this variation site is associated with CAD in elderly Chinese Han men.