肾素-血管紧张素系统基因多态性与高血压及心肌梗死和中风家族史的关系：PEGASE研究。严重至中度原发性高血压基因研究项目。

Gene polymorphisms of the renin-angiotensin system in relation to hypertension and parental history of myocardial infarction and stroke: the PEGASE study. Projet d'Etude des Gènes de l'Hypertension Artérielle Sévère à modérée Essentielle.

作者信息

Tiret L, Blanc H, Ruidavets J B, Arveiler D, Luc G, Jeunemaitre X, Tichet J, Mallet C, Poirier O, Plouin P F, Cambien F

机构信息

INSERM U258, Hôpital Broussais, Paris, France.

出版信息

J Hypertens. 1998 Jan;16(1):37-44. doi: 10.1097/00004872-199816010-00007.

DOI:10.1097/00004872-199816010-00007

PMID:9533415

Abstract

OBJECTIVE

To investigate a possible involvement of polymorphisms of the renin-angiotensin system in predisposition to moderate and severe hypertension and their relationship to parental histories of myocardial infarction and stroke.

METHODS

Hypertensive cases (453 men, 326 women) were patients followed up by general practitioners for established hypertension. Inclusion criteria were an age of onset of hypertension < or = 60 years and a diastolic blood pressure > or = 105 mmHg without antihypertensive medication or > or = 100 mmHg under treatment. Normotensive controls were selected from population-based samples (362 men) and during a preventative medicine visit (170 women). Polymorphisms of the angiotensinogen gene (AGT M235T and T174M), the angiotensin I converting enzyme gene (ACE I/D), and the angiotensin II type 1 receptor gene (AGT1R A1166C) were investigated.

RESULTS

The AGTT235 allele prevalence was higher among male hypertensive cases than it was among controls (0.46 versus 0.40, P = 0.01) and a similar trend was observed with female cases whose hypertension had been diagnosed before they were aged 45 years (0.44 versus 0.38, P = 0.20). The AGT1R C1166 allele prevalence was higher among female hypertensives than it was among controls (0.30 versus 0.23, P = 0.03) but no such difference was observed for men. The AGT T174M and ACE I/D polymorphisms were not associated with hypertension. Hypertensive patients reporting a parental history of myocardial infarction before age 60 years had a higher prevalence of the ACE D allele than did those without such a parental history (0.68 versus 0.56, P = 0.01). The ACE D allele prevalence was also greater among patients reporting a parental history of stroke incidence before age 65 years (0.66 versus 0.57, P = 0.05).

CONCLUSIONS

These results support the hypothesis that the AGT gene plays a role in predisposition to hypertension and that the ACE gene plays a role in predisposition to acute ischemic events.

摘要

目的

研究肾素 - 血管紧张素系统多态性在中重度高血压易感性中的可能作用及其与心肌梗死和中风家族史的关系。

方法

高血压病例（453名男性，326名女性）为经全科医生随访确诊的高血压患者。纳入标准为高血压发病年龄≤60岁，未服用抗高血压药物时舒张压≥105 mmHg或治疗期间舒张压≥100 mmHg。正常血压对照组从基于人群的样本中选取（362名男性）以及在预防医学就诊时选取（170名女性）。研究血管紧张素原基因（AGT M235T和T174M）、血管紧张素I转换酶基因（ACE I/D）和血管紧张素II 1型受体基因（AGT1R A1166C）的多态性。

结果

男性高血压病例中AGT T235等位基因频率高于对照组（0.46对0.40，P = 0.01），45岁前诊断为高血压的女性病例也观察到类似趋势（0.44对0.38，P = 0.20）。女性高血压患者中AGT1R C1166等位基因频率高于对照组（0.30对0.23，P = 0.03），但男性未观察到这种差异。AGT T174M和ACE I/D多态性与高血压无关。有60岁前心肌梗死家族史的高血压患者ACE D等位基因频率高于无此类家族史者（0.68对0.56，P = 0.01）。有65岁前中风家族史的患者中ACE D等位基因频率也更高（0.66对0.57，P = 0.05）。