AT_1R基因多态性与原发性高血压中医证型及降压中药疗效的关系

Relationship of the A1166C Polymorphism of AT_1R Gene with TCM Syndrome and Efficacy of Chinese Hypotensor in Patients with Essential Hypertension

目的观察国人原发性高血压(essentialhypertension,EH)患者血管紧张素Ⅱ(AngⅡ)一型受体(AT1R)基因A1166C多态性的分布,及其与高血压中医辨证分型和降压药物疗效的关系。方法测定206例汉族EH患者和86名汉族健康人的血压、体重指数、空腹血糖、胆固醇、甘油三酯浓度以及血浆AngⅡ、内皮素(ET)、降钙素基因相关肽(CGRP)水平。用盐析法提取外周血白细胞DNA,PCR加限制性酶切方法检测AT1R的1166位基因突变。根据高血压中医辨证标准对206例高血压病患者进行辨证分型,比较各中医证型的基因分布;分别用清心胶囊和卡托普利治疗阴虚阳亢型高血压患者34例与32例,观察其降压效果与基因型分布的关系。结果(1)高血压组除收缩压、舒张压显著高于正常对照组外,体重指数、空腹血糖及血脂、血浆相关激素水平两组比较差异无显著性;(2)EH患者AT1R基因AC加CC基因型的比例为0·126,较正常对照组0·047显著增高(P<0·01),C等位基因分布频率也明显高于正常对照组,分别为0·068、0·023(P<0·05);而男性与女性之间,AT1R基因型和等位基因分布频率,差异均无显著性;(3)基因分型与临床表型:AA基因型与AC加CC基因型间收缩压、舒张压、血糖、血脂、血浆AngⅡ、ET、CGRP水平经t检验,差异无显著性(P>0·05);(4)基因分型与中医分型:高血压病各证型中AA基因型与AC加CC基因型分布,差异亦无显著性(P>0·05);(5)基因分型与降压疗效:卡托普利和清心胶囊对不同基因型高血压患者均有效,各治疗组中AA与AC加CC基因型高血压患者降压效果相近。结论在中国汉族人群中,AC基因型与原发性高血压有关,C等位基因可能是高血压的一个易感基因;而高血压病中医辨证分型可能与是否携带C等位基因无关,清心胶囊和卡托普利的降压效应与是否携带C1166等位基因无关。在不同基因型的EH患者中,其血压、血糖、血脂、血浆AngⅡ、ET、CGRP未见明显差异,提示基因型对高血压的影响可能未通过糖脂代谢、血浆ET、CGRP、AngⅡ系统。

Objective To investigate the polymorphic distribution of the A1166C, the angiotensin Ⅱ type I receptor （AT1R） gene, in the Chinese people with essential hypertension （EH）, and to study the relationship of A1166C with the TCM syndrome types and the efficacy of hypotensor. Methods Blood pressure （BP）, body weight index （BWI）, fasting blood glucose （FBG）, cholesterol （Ch）, concentration of triglyceride, levels of serum plasma Ang Ⅱ , endothelin （ET） and calcitonin-gene related peptide （CGRP） in 206 patients with EH and 86 health subjects of Chinese nationality were determined. DNA of peripheral white blood cells were extracted by salting out method and the polymorphism of AT1R gene A1166C was assessed by PCR and limited enzymatic segmentation. The 206 EH patients were differentiated into different types according to TCM syndrome differentiation, and the gene distribution appeared in each TCM syndromes was compared. Qingxin Capsule （QC） or captopril was used respectively to treat 34 and 32 patients with hypertension of Yin-deficiency and excessive Yang type to observe the relationship between the hypotensive effect of treatment and the distribution of gene types. Results （1） No significant difference was found in BWt, FBG, blood lipid or serum related hormones, only the difference in systolic and diastolic pressure was shown between the hypertension group and the control group. （2） The rate of AT1R AC plus CC gene type in EH patients was 0. 126, which was significantly higher than that in the normal control group （0.047, P 〈0.01）. The frequency of C allele distribution was obviously higher than that in the normal control group （0.068 vs0.023, P〈0.05）. No significant difference was found in AT1R gene types or frequency of allele distribution between different sexes （male and female）. （3） Analysis on relationship between gene types and clinical phenotype showed that no significant difference was found in systolic pressure, diastolic pressure, blood glucose, blood lipid, plasma Ang Ⅱ , ET, or CGRP between patients with AA gene type and with AA plus CC gene type by t test （P 〉0.05）. （4） Analysis on relationship between gene type and TCM syndrome type showed that the distribution of AA gene type and AA plus CC type was insignificantly different in patients with various TCM syndrome types. （5） Analysis on relationship between gene type and hypotensive effect of treatments showed that both QC and captopril were effective to patients with hypertension of different gene types. The hypotensive effect of either was similar in spite of what gene types the patients with. Conclusion A1166C gene type is related to EH in the Chinese, C allele might a susceptible gene to hypertension, while TCM syndrome type of EH patients might not be related to whether C allele was borne. The hypotensive effect of QC or captopril was not related to whether C1166 allele was borne. No significant difference of blood pressure, blood glucose, blood lipid, plasma Ang Ⅱ , ET, or CGRP in patients with different gene types, which suggested the effect of gene types on hypertension might not be by path of glucose or lipid metabolism, ET, CGRP or plasma Ang Ⅱ system.