AT1R基因位点与环境因素交互作用对原发性高血压证候形成的影响

Correlation between AT1R gene polymorphism and environmental factors and its implication for TCM patterns in essential hypertension

目的通过分析血管紧张素II-1型受体(AT1R)2个基因位点与内外环境因素的交互作用,探讨AT1R基因多态性与环境因素交互作用对原发性高血压(EH)不同证型患者证候形成的影响。方法筛选4型EH患者各100例,健康对照组100例。用多重高温连接酶检测反应基因分型技术(i MLDR)检测AT1R基因A1166C及T573C位点多态性;用多因素降维分析法(MDR)分析环境因素与AT1R基因多态性交互作用对EH不同证型的影响。结果痰湿壅盛组和阴阳两虚组的最佳模型为低密度脂蛋白(LDL-C)、体重指数(BMI)、食盐摄入量、饮酒、AT1R基因T573C位点的联合作用;肝火亢盛组的最佳模型为LDL-C与BMI的联合作用;阴虚阳亢组的最佳模型为饮食习惯的单因素模型。痰湿壅盛证中饮酒、食盐摄入量及LDL-C与T573C位点交互作用更密切;阴阳两虚证饮食习惯、BMI及LDL-C与T573C位点的交互作用更密切。结论内外环境因素之间的交互作用可能是原发性高血压不同证候形成内在因素;其中AT1R基因T573C位点与环境因素交互作用可能对原发性高血压痰湿壅盛证及阴阳两虚证形成具有重要作用。

Objective To reveal the correlation between angiotensin II-l receptor（ AT1R） gene polymorphism and environmental factors and its implication for different TCM patterns in essential hypertension by analyzing the correlation between two genetic loci of AT1 R and environmental factors. Methods Four groups of EH patients with different TCM patterns and one healthy control group were selected（ n = 100 in each group）. Gene locus polymorphism of A1166 C and T573 C of AT1 R gene was detected by using multiple high temperature ligase detection reaction genotyping technique（ i MLDR） while the effects of correlation between the AT1 R gene polymorphism and environmental factors on different TCM patterns in essential hypertension were assessed by using Multifactor Dimensionality Reduction（ MDR）. Results The results indicated the optimal diagnostic model of excessive phlegm-dampness pattern and yin-yang deficiency pattern were the combination of low-density lipoprotein cholesterol（ LDL-C）,body mass index（ BMI）,salt intake and alcohol consumption with T573 C locus of AT1 R gene. The optimal diagnostic model of liver-fire hyperactivity pattern was the combination of LDL-C and BMI. The optimal diagnostic model of yin deficiency with yang hyperactivity pattern was mono-factor model of dietary habit. It showed that there was a close correlation among LDL-C,salt intake,alcohol consumption with AT1 R T573C gene locus in excessive phlegm-dampness pattern. Meanwhile,it also showed a close interaction of LDL-C,BMI,and dietary habit with AT1 R T573C gene locus in yin-yang deficiency group. Conclusion Correlation between internal and external factors of human may be used to signify different patterns of EH. The correlation between environment factors and T573 C locus of AT1 R gene may be important to the formation of excessive phlegm-dampness pattern and yin-yang deficiency pattern.