汉族人群乙醛脱氢酶2基因 Glu504 Lys 多态性与原发性高血压患者颈动脉内膜中层厚度增厚的关系及其机制研究

摘要

目的：探讨汉族人群ALDH2基因Glu504Lys多态性与原发性高血压（Essential hypertension，EH）患者颈动脉内膜中层厚度（ CIMT）增厚之间的关系及其作用机制。方法选择四川省人民医院进行体检的EH患者414例，根据CIMT厚度分为CIMT增厚组与CIMT正常组，对CIMT增厚组行肱动脉血流介导的内皮依赖性舒张功能（ FMD）检测；分析不同基因型与CIMT增厚的关系及CIMT增厚组中不同基因型携带者与FMD的相关性。结果 CIMT增厚组AG型、AA型、AA／AG基因型及A等位基因频率显著高于CIMT正常组，差异均有统计学意义（均P＜0．05）。Logistic回归分析显示ALDH2基因Glu504Lys AA／AG基因与CIMT增厚相关。多元线性回归分析发现，CIMT增厚组中ALDH2基因Glu504 Lys AA／AG基因型与FMD值的降低独立相关；将FMD作为变量纳入回归分析后，ALDH2基因多态性与CIMT的相关性较之前明显降低。结论汉族人群ALDH2基因Glu504 Lys多态性与EH患者CIMT增厚存在相关性，ALDH2基因Glu504 Lys突变可能通过使血管EDD发生障碍导致EH发生CIMT增厚。%Objective To explore the relationship and its mechanism between Glu 504Lys polymorphism of aldehyde dehydro-genase 2 (ALDH2) in Han population and thickening of the carotid intima-media thickness (CIMT) in essential hypertension (EH) patients.Methods We selected 414 EH patients in Sichuan Province People 's Hospital and divided into CIMT thickening group and CIMT normality group.The endothelium dependent dilation function was detected by brachial artery flow -mediated dilation (FMD) in the patients with CIMT thickening group .The relationships between different genotypes and thickening of the CIMT and between differ -ent genotypes and FMD in the EH patients were statistically analyzed .Results The frequencies of AG type ,AA type,AA/AG type and A allele in the CIMT thickening group were significantly higher than those in the normal CIMT group ( P<0.05 ) .Logistic regression a-nalysis demonstrated that AA/AG gene type of ALDH2 Glu504Lys was related to CIMT thickening .Multiple linear regression analysis showed that AA/AG gene type of ALDH2 Glu504Lys was independently related to decreased FMD in the EH patients with CIMT thick-ness.However,the correlation between ALDH2 gene Glu504Lys polymorphism and EH patients combined with increased CIMT was low-ered after including FMD as an independent variable in logistic regression analysis .Conclusion ALDH2 gene Glu504 Lys polymor-phism in Han population was associated with thickening of CIMT in EH patients .The mutations of ALDH2 gene Glu504Lys lead to CI-MT thickening in EH patients through abnormalities of vascular EDD .