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[血管紧张素Ⅱ 1型受体基因A1166C多态性与原发性高血压患者中医证型及降压中药疗效的关系]

[Relationship of the A1166C polymorphism of ATI R gene with TCM syndrome and efficacy of Chinese hypotensor in patients with essential hypertension].

作者信息

Lu Quan-Sheng, Lei Yan, Chen Ke-Ji

机构信息

Xiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing. China Academy of Traditional Chinese Medicine, Beijing.

出版信息

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2005 Aug;25(8):682-6.

Abstract

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 BWI, 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 vs 0.023, 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.

摘要

目的

探讨血管紧张素Ⅱ 1型受体(AT1R)基因A1166C多态性在中国原发性高血压(EH)患者中的分布情况,并研究A1166C与中医证型及降压疗效的关系。

方法

测定206例EH患者和86例中国籍健康受试者的血压(BP)、体重指数(BWI)、空腹血糖(FBG)、胆固醇(Ch)、甘油三酯浓度、血清血管紧张素Ⅱ(AngⅡ)、内皮素(ET)及降钙素基因相关肽(CGRP)水平。采用盐析法提取外周血白细胞DNA,通过聚合酶链反应(PCR)和限制性酶切分析AT1R基因A1166C的多态性。将206例EH患者按中医辨证分为不同证型,比较各中医证型中基因分布情况。分别用清心胶囊(QC)或卡托普利治疗34例和32例阴虚阳亢型高血压患者,观察治疗降压效果与基因分型的关系。

结果

(1)高血压组与对照组在BWI、FBG、血脂及血清相关激素方面无显著差异,仅收缩压和舒张压有差异。(2)EH患者中AT1R基因AC+CC基因型频率为0.126,显著高于正常对照组(0.047,P<0.01)。C等位基因分布频率明显高于正常对照组(0.068对0.023,P<0.05)。不同性别(男、女)间AT1R基因分型及等位基因分布频率无显著差异。(3)基因分型与临床表型关系分析显示,AA基因型与AA+CC基因型患者的收缩压、舒张压、血糖、血脂、血浆AngⅡ、ET或CGRP经t检验无显著差异(P>0.05)。(4)基因分型与中医证型关系分析显示,各中医证型患者中AA基因型与AA+CC基因型分布无显著差异。(5)基因分型与治疗降压效果关系分析显示,QC和卡托普利对不同基因分型的高血压患者均有效。无论患者基因分型如何,二者降压效果相似。

结论

A1166C基因型与中国人的EH相关,C等位基因可能是高血压的易感基因,而EH患者的中医证型可能与是否携带C等位基因无关。QC或卡托普利的降压效果与是否携带C1166等位基因无关。不同基因分型患者的血压、血糖、血脂、血浆AngⅡ、ET或CGRP无显著差异,提示基因分型对高血压的影响可能不是通过糖脂代谢、ET、CGRP或血浆AngⅡ系统途径。

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