Xu Limin, Zhou Jianqing, Huang Stephanie, Huang Yi, LE Yanping, Jiang Danjie, Wang Feiming, Yang Xi, Xu Weifeng, Huang Xiaoyan, Dong Changzheng, Zhang Lina, Ye Meng, Lian Jiangfang, Duan Shiwei
School of Medicine, The Affiliated Hospital, Ningbo University, Ningbo, Zhejiang 315211;
Exp Ther Med. 2013 Mar;5(3):742-750. doi: 10.3892/etm.2013.911. Epub 2013 Jan 21.
Previous genome-wide association studies (GWAS) have revealed seven single nucleotide polymorphisms (SNPs) that affect lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity or levels in American and European individuals. A total of 290 coronary heart disease (CHD) patients, 198 non-CHD patients and 331 unrelated healthy volunteers were recruited for the present case-control study of Han Chinese. Four SNPs (rs964184 of ZNF259, rs7528419 of CELSR2 and rs7756935 and rs1805017 of PLA2G7) were shown to be significantly associated with CHD. The rs964184-G allele of the ZNF259 gene was identified as a risk factor of CHD in females (odds ratio (OR) =1.49, 95% confidence interval (CI) =1.00-2.22, P=0.05). The rs7528419-G allele of the CELSR2 gene was protective against CHD in males (OR=0.48, 95% CI=0.25-0.93, P=0.04). The other two alleles (rs7756935-C and rs1805017-A) of the PLA2G7 gene acted as protective factors against CHD in females (rs7756935-C: OR=0.59, 95% CI=0.35-1.00, P=0.05; rs1805017-A: OR=0.51, 95% CI=0.28-0.93, P=0.03). Moreover, rs1805017 of the PLA2G7 gene was associated with the severity of CHD only in females (r(2)=0.02, P=0.04). We identified four Lp-PLA(2)-associated SNPs significantly associated with CHD in a Han Chinese population. Specifically, rs7528419 was protective factor against CHD in males, while the other two SNPs (rs7756935 and rs1805017 of the PLA2G7 gene) were protective factors against CHD in females and rs964184 of the ZNF259 gene was regarded as a risk factor for CHD in females.
此前的全基因组关联研究(GWAS)已揭示出7个单核苷酸多态性(SNP),这些多态性会影响美国和欧洲人群中脂蛋白相关磷脂酶A2(Lp-PLA2)的活性或水平。本病例对照研究招募了290名冠心病(CHD)患者、198名非CHD患者和331名无血缘关系的健康志愿者,研究对象为汉族人群。结果显示,4个SNP(ZNF259基因的rs964184、CELSR2基因的rs7528419以及PLA2G7基因的rs7756935和rs1805017)与CHD显著相关。ZNF259基因的rs964184 - G等位基因被确定为女性CHD的危险因素(优势比(OR)=1.49,95%置信区间(CI)=1.00 - 2.22,P = 0.05)。CELSR2基因的rs7528419 - G等位基因对男性CHD具有保护作用(OR = 0.48,95% CI = 0.25 - 0.93,P = 0.04)。PLA2G7基因的其他两个等位基因(rs7756935 - C和rs1805017 - A)对女性CHD起到保护作用(rs7756935 - C:OR = 0.59,95% CI = 0.35 - 1.00,P = 0.05;rs1805017 - A:OR = 0.51,95% CI = 0.28 - 0.93,P = 0.03)。此外,PLA2G7基因的rs1805017仅在女性中与CHD的严重程度相关(r2 = 0.02,P = 0.04)。我们在汉族人群中鉴定出4个与Lp-PLA2相关的SNP,它们与CHD显著相关。具体而言,rs7528419是男性CHD的保护因素,而其他两个SNP(PLA2G7基因的rs7756935和rs1805017)是女性CHD的保护因素,ZNF259基因的rs964184被视为女性CHD的危险因素。