Renin‐angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition
Renin‐angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition
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肾素-血管紧张素系统基因多态性影响血压和对血管紧张素转换酶抑制的反应
DOI：
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发表时间：
1995
影响因子：
4.9
通讯作者：
J. E. Claire Dickerson
中科院分区：
文献类型：
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作者：
A. Hingorani;P. Stevens;Morris J. Brown;H. Jia;R. Hopper;J. E. Claire Dickerson
目的探讨血管紧张素转换酶（ACE）、血管紧张素原（AGT）和1型血管紧张素Ⅱ（AT1R）基因多态性与高血压患者血压定量变异和ACE抑制剂降压反应的关系。设计和方法：我们给125例既往未经治疗的原发性高血压患者使用ACE抑制剂进行单药治疗。检测外周血白细胞DNA中ACE插入和缺失基因型、AGT M235T和AT1R A1166±C多态性。通过方差分析和多元回归分析，校正年龄、性别、体重指数、酒精摄入量和（如适用）治疗前血压，检测基因型对治疗前血压和ACE底物诱导的血压降低的影响。结果ACE和AT1R基因型是治疗前收缩压和舒张压的独立预测因子，两个基因位点之间存在明显的交互作用。尽管AGT基因型不影响该人群的治疗前血压，但它是ACE抑制后血压反应的独立预测因素。结论ACE和AT1R基因位点（分别位于染色体17 q和3q）可能携带影响高血压人群血压变异的等位基因，两个位点之间可能存在上位性相互作用。AGT T235等位基因似乎不是该组血压变化的标志物，但位于AGT基因内或附近的染色体1q上的变异可能导致对ACE抑制的血压反应的个体差异。在原发性高血压患者中，ACE抑制剂反应的差异似乎部分由遗传决定。
Objectives To investigate the relationship between polymorphisms in the angiotensin converting enzyme (ACE), angiotensinogen (AGT) and type 1 angiotensin-II (AT1R) genes and (1) quantitative variations in blood pressure and (2) the blood pressure response to ACE inhibition in a hypertensive cohort. Design and methods We administered monotherapy with ACE inhibitors to 125 previously untreated essential hypertensives. Genotypes for ACE insertion and deletion, AGT M235T and AT1R A1166±C polymorphisms were determined in DNA extracted from peripheral blood leucocytes. The influence of genotype on pretreatment blood pressure and the ACE inhibitor-induced decrease in blood pressure was tested by analysis of variance and multiple regression analysis, adjusting for age, sex, body mass index, alcohol intake and, where appropriate, pretreatment blood pressure. Results ACE and AT1R genotypes were independent predictors of pretreatment systolic and diastolic blood pressure, with an apparent interaction between these two gene loci. Although it did not influence pretreatment blood pressure in this population, AGT genotype was an independent predictor of the blood pressure response to ACE inhibition. Conclusions The ACE and AT1R gene loci (chromosomes 17q and 3q, respectively) may carry alleles influencing blood pressure variation in this hypertensive population, with a possible epistatic interaction between the two loci. The AGT T235 allele does not appear to be a marker for blood pressure variation in this group, but variants on chromosome 1q lying in or near the AGT gene may contribute to individual differences in the blood pressure response to ACE inhibition. Among essential hypertensives, differences in the ACE inhibitor response appear, in part, to be genetically determined.