摘要
目的探讨与脑小血管病有关的易感基因及基因预测模型。 方法对共792例4组研究对象的脱氧核糖核酸（deoxyribonucleic acid，DNA）样本应用SNaPshot单核苷酸多态性（single nucleotide polymorphisms，SNP）分型技术进行19个候选基因55个SNP位点分型，在5种遗传模型下对脑小血管病与非卒中对照组个体之间分析，并进行各组之间差异显著性检验及危险因素分析。应用了SAS软件构建预测模型。结果脑小血管病与非卒中对照组个体差异性检验，肌球蛋白轻链激酶基因（myosin light chain kinase，MYLK）SNP位点rs2222823杂合子（A/T）的优势比（odds ratio，OR）为0.52[95%可信区间（confidence interval，CI）（0.35～0.79），P=0.002，校正P=0.031]；细胞周期依赖性激酶抑制基因2A（inhibitor of cdk 4/alternative reading frame，INK4/ARF）SNP位点rs2811712杂合子（C/T）的OR值为1.75[95%CI 1.13～2.71，P=0.004，校正P=0.050]。脑小血管病与高血压性脑出血患者差异性检验， rs2222823位点的P值为0.035。脑小血管病与大动脉硬化性脑血管病患者差异性检验，非糖尿病患者及饮酒患者在rs2222823位点P值分别为0.012和0.018；高脂血症及饮酒患者在rs2811712位点P值分别为0.029和0.04。构建预测模型的基尼指数为0.442。 结论 MYLK和INK4/ARF基因与中国人群中动脉硬化性脑小血管病有相关性，rs2222823杂合子（A/T）有减缓脑小血管病患病率作用，而rs2811712杂合子（C/T）对脑小血管病的患病率具有促进作用。
Objective To investigate the association between cerebral small vessel disease （CSVD） and susceptibility loci and candidate genes. Methods Seven hundred and ninety-two subjects admitted to Beijing Tiantan Hospital were divided into four groups. Fifty-five single nucleotide polymorphisms （SNPs） in 19 genes were genotyped using Multiplex Snapshot assay. Each SNP was ifrst examined between the groups S and C in ifve genetic models. The signiifcant SNP loci were further analyzed in comparing S with L and H, respectively. Subgroup analysis was also performed for each risk-factor category. The SAS software was applied to build predictive models. 〈br〉 Results rs2222823 and rs2811712 were found to be significantly associated with CSVD after multiple-testing adjustment. The heterozygote （A/T） of rs2222823 of myosin light chain kinase （MYLK） has an odds ratio of 0.52 （95%conifdence interval [CI] [0.35～0.79], P=0.002, adjusted P=0.03） when compared with homozygote. The heterozygote （C/T） of rs2811712 of inhibitor of cdk 4/alternative reading frame （INK4/ARF） has an odds ratio of 1.75 （95%CI [1.13～2.71], P=0.004, adjusted P=0.05）. The SNP rs2222823 was signiifcant （P=0.035） in comparing S with H. In comparing S vs. L, it is signiifcant for the subgroups of patients without diabetes （P=0.012） and drinking （P=0.018）. rs2811712 was signiifcant in comparing S with L for the subgroups of patients with hyperlipidemia （P=0.029） and drinking （P=0.04）. The Gini of predictive models was 0.442.Conclusion The heterozygote （A/T） at the rs2222823 SNP locus decreases the risk of having CSVD, while the heterozygote （C/T） at the rs2811712 SNP locus increases the risk, suggesting that the MYLK and INK4/ARF are the associated genes of CSVD in Han Chinese population.
出处
《中国卒中杂志》
2014年第9期743-750,共8页
Chinese Journal of Stroke
基金
北京市脑血管病临床数据和样本资源库建设(D09050703560904)
首都医科大学基础-临床科研合作基金(14JL54)
北京市教育委员会科技计划重点项目(KM201410025028)
脑血管病转化医学北京市重点实验开放课题资助
国家重点基础研究发展计划(973计划)资助项目(2009CB521905)
关键词
脑小血管病
易感基因
杂合子
Cerebral small vessel disease
Susceptibility genes
Heterozygote genotype
