Susceptibility Genes and Prediction Model of Cerebral Small Vessel Disease in Chinese Population

Abstract

Abstract:

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 first examined between the groups S and C in five genetic models. The significant 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. 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% confidence 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 significant (P =0.035) in comparing S with H. In comparing S vs. L, it is significant for the subgroups of patients without diabetes (P =0.012) and 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 first examined between the groups S and C in five genetic models. The significant 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. 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% confidence 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 significant (P =0.035) in comparing S with H. In comparing S vs. L, it is significant for the subgroups of patients without diabetes (P =0.012) and

Key words: Cerebral small vessel disease; Susceptibility genes; Heterozygote genotype

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。

关键词: 脑小血管病; 易感基因; 杂合子

LI Wei, HU Bo, LI Gui-Lin, et al.. Susceptibility Genes and Prediction Model of Cerebral Small Vessel Disease in Chinese Population[J]. Chinese Journal of Stroke, 2014, 9(09): 743-750.

李伟，胡波，李桂林，等. 中国人群中动脉硬化性脑小血管病易感基因及预测模型的研究[J]. 中国卒中杂志, 2014, 9(09): 743-750.

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