烟酰胺磷酸核糖转移酶在表观遗传学中与脑梗死的相关性研究

Relationship between nicotinamide phosphoribosyltransferase and cerebral infarction in epigenetics

目的评估烟酰胺磷酸核糖转移酶(NAMPT)基因启动子区甲基化水平与脑梗死患者及相关临床指标的相关性。方法使用病例对照的方法,选取152例(男112例,女40例)确诊脑梗死患者为病例组,152例(男112例,女40例)健康人为对照组,提取基因组DNA,经亚硫酸转化后使用荧光定量甲基化特异性PCR(qMSP)测定受试者的NAMPT基因启动子区DNA甲基化水平。结果用卡方检验对两组进行分析,病例组NAMPT甲基化率为24.59%,对照组为19.69%;按性别分亚组后,男性中两组甲基化率分别为30.23%、23.08%,女性中两组甲基化率均为11.11%,差异无统计学意义。然而,根据是否甲基化分组后分析,NAMPT甲基化组受试者的平均年龄水平显著高于非甲基化组[(60.92±13.97)比(52.75±11.98),t=4.443,P<0.05),NAMPT甲基化组的C反应蛋白(CRP)水平显著高于非甲基化组[(11.12±7.16)比(4.87±2.71),t=3.429,P=0.001]。结论外周血NAMPT启动子区高甲基化水平不能作为脑梗死的1个标志物,NAMPT基因甲基化水平与炎性指标和年龄、衰老有着显著的关联性,值得进一步研究。

Objective To evaluate the correlation between methylation level of nicotinamide phosphoryltransferase (NAMPT) promoter region and cerebral infarction patients and related clinical indexes. Methods Using the case-control method, 152 cases (112 males and 40 females) with confirmed ischemic stroke were selected as Case group, 152 healthy Persons (112 males and 40 females) as control group, after extraction of genome DNA, the DNA methylation level of NAMPT gene promoter was measured by fluorescence quantitative methylation specific PCR (qMSP) after the sulfite transformation. Results Chi-square test showed that the methylation rate of NAMPT in the case group was 24.59%. The control group was 19.69%. After sex subgroup, the rate of methylation in male group was 30.23% and 23.08% and that in female group was 11.11%, both of them was not found significant difference. However, after grouping according to whether or not methylatedthe, average age of the NAMPT hypermethylation group was significantly higher than that in the non methylation group [(60.92±13.97) vs (52.75±11.98), t=4.443,P<0.05), the level of C reactive protein (CRP) in the NAMPT methylation group was significantly higher than that in the non methylation group [(11.12±7.16) vs (4.87±2.71),t= 3.429,P=0.001)]. Conclusion The hypermethylation level of NAMPT promoter in peripheral blood can not be used as a marker of cerebral infarc?tion,the methylation level of NAMPT gene was significantly correlated with inflammatory markers, age and aging.