Hou Liping, Chen Shufeng, Yu Hongjiang, Lu Xiangfeng, Chen Jianhong, Wang Laiyuan, Huang Jianfeng, Fan Zhongjie, Gu Dongfeng
Department of Evidence Based Medicine and Division of Population Genetics, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, 100037 Beijing, China.
Hum Genet. 2009 Feb;125(1):11-20. doi: 10.1007/s00439-008-0587-4. Epub 2008 Nov 26.
The human PLA2G7 gene encodes lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an emerging risk factor for cardiovascular diseases. In the present study, seven single nucleotide polymorphisms (SNPs) in the PLA2G7 gene were genotyped in 827 patients with coronary heart disease (CHD), of which 512 were patients with myocardial infarction (MI), and 947 age- and gender-matched controls in a Chinese Han population. Plasma Lp-PLA(2) activity was measured in 416 randomly selected controls and 689 randomly selected CHD patients, including 423 MI patients. Lp-PLA(2) activity in CHD and MI cases was significantly higher (233.42+/-57.66 and 234.27+/-59.51 nmol ml(-1) min(-1), respectively) than in controls (211.47+/-58.61 nmol ml(-1) min(-1)). After adjusting for traditional risk factors by logistic regression, the odds ratios for CHD and MI per 1 standard deviation increment of Lp-PLA(2) activity were 1.27 (95% CI, 1.07-1.50) and 1.27 (95% CI, 1.05-1.54), respectively. Both single SNP analysis and haplotype analysis showed that the V279F and I198T polymorphisms were significantly associated with the reduced Lp-PLA(2) activity, but neither was associated with increased CHD risk. Both univariate and multivariate analyses, adjusting effects of conventional factors, indicated that the rs13210554 T allele increased the risk of MI in this Chinese Han population. In summary, an independent association of increased plasma Lp-PLA(2) activity with CHD and MI existed in this Chinese Han Population. Although V279F and I198T mutations significantly decreased the activity of Lp-PLA(2), only the promoter rs13210554 polymorphism was associated with MI. Lp-PLA(2) activity appears to influence the CHD and MI risk in Chinese Han population.
人类PLA2G7基因编码脂蛋白相关磷脂酶A2(Lp-PLA2),这是一种新出现的心血管疾病风险因素。在本研究中,对中国汉族人群中的827例冠心病(CHD)患者(其中512例为心肌梗死患者)以及947例年龄和性别匹配的对照者进行了PLA2G7基因中7个单核苷酸多态性(SNP)的基因分型。在416例随机选择的对照者和689例随机选择的CHD患者(包括423例心肌梗死患者)中测量了血浆Lp-PLA2活性。CHD和心肌梗死病例中的Lp-PLA2活性(分别为233.42±57.66和234.27±59.51 nmol ml-1 min-1)显著高于对照者(211.47±58.61 nmol ml-1 min-1)。通过逻辑回归调整传统风险因素后,Lp-PLA2活性每增加1个标准差,CHD和心肌梗死的比值比分别为1.27(95%CI,1.07-1.50)和1.27(95%CI,1.05-1.54)。单SNP分析和单倍型分析均显示,V279F和I198T多态性与Lp-PLA2活性降低显著相关,但两者均与CHD风险增加无关。单因素和多因素分析(调整传统因素的影响)均表明,rs13210554 T等位基因增加了中国汉族人群中心肌梗死的风险。总之,在中国汉族人群中,血浆Lp-PLA2活性升高与CHD和心肌梗死存在独立关联。虽然V279F和I198T突变显著降低了Lp-PLA2的活性,但只有启动子rs13210554多态性与心肌梗死相关。Lp-PLA2活性似乎影响中国汉族人群中的CHD和心肌梗死风险。