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血管紧张素原基因的M235→T多态性可预测老年人患高血压的风险。

M235-->T polymorphism of the angiotensinogen gene predicts hypertension in the elderly.

作者信息

Johnson A G, Simons L A, Friedlander Y, Simons J, Davis D R, MaCallum J

机构信息

University Department of Medicine, Princess Alexandra Hospital & University of Queensland, Brisbane, Australia.

出版信息

J Hypertens. 1996 Sep;14(9):1061-5. doi: 10.1097/00004872-199609000-00003.

Abstract

OBJECTIVE

To determine whether the M235-->T polymorphism (exon 2) of the angiotensinogen gene is associated with hypertension in elderly patients with isolated systolic hypertension [ISH: systolic blood pressure (SBP) > or = 160 mmHg, diastolic blood pressure (DBP) < 90 mmHg) or systolic-diastolic hypertension (SDH: DBP > or = 90 mmHg, SBP > or = 160 mmHg) compared with normotensive controls (SBP < 160 mmHg, DBP < 90 mmHg).

DESIGN

A case-control study in 769 non-institutionalized, elderly (aged > or = 60 years; female:male ratio 0.85) residents of Dubbo, New South Wales.

METHODS

Individuals were classified as having ISH (n = 171), having SDH (n = 218) and being normotensive controls (n = 366) with age and sex matching. MM, TT and MT genotypes were determined by a nested polymerase chain reaction strategy using DNA extracted from serum. The prediction of ISH or SDH by genotype or allele was examined in a multiple-logistic regression model that controlled for various confounders.

RESULTS

SBP (mean +/- SD, mmHg)/DBP (mean +/- SD, mmHg) was 176 +/- 16/79 +/- 8 in the ISH group, 167 +/- 23/97 +/- 7 in the SDH group and 134 +/- 14/74 +/- 9 in the normotensive control group. The frequencies of M and T alleles in the normal population (0.69 and 0.31, respectively) were altered significantly in the ISH group (0.61 and 0.39, respectively; chi 2 = 6.0, P < 0.02) and the SDH group (0.62 and 0.38, respectively; chi 2 = 6.0, P < 0.02). The presence of the TT genotype predicted both ISH (odds ratio 1.9, 95% confidence interval 1.1-3.3) and SDH (1.7, 1.0-3.0) as did that of the T allele (ISH: 1.3, 1.0-1.7; SDH: 1.3, 1.0-1.7).

CONCLUSIONS

The M235-->T polymorphism may be a marker for both forms of hypertension in the elderly. Whether the TT genotype represents a genetic risk factor for the development of hypertension in later life requires confirmation.

摘要

目的

确定血管紧张素原基因M235→T多态性(第2外显子)与老年单纯收缩期高血压患者[ISH:收缩压(SBP)≥160 mmHg,舒张压(DBP)<90 mmHg]或收缩期-舒张期高血压患者(SDH:DBP≥90 mmHg,SBP≥160 mmHg)的高血压是否相关,并与血压正常的对照组(SBP<160 mmHg,DBP<90 mmHg)进行比较。

设计

对新南威尔士州达博市769名非机构化老年(年龄≥60岁;女性与男性比例为0.85)居民进行病例对照研究。

方法

根据年龄和性别匹配,将个体分为ISH组(n = 171)、SDH组(n = 218)和血压正常对照组(n = 366)。采用巢式聚合酶链反应策略,使用从血清中提取的DNA确定MM、TT和MT基因型。在控制各种混杂因素的多因素逻辑回归模型中,研究基因型或等位基因对ISH或SDH的预测作用。

结果

ISH组的SBP(均值±标准差,mmHg)/DBP(均值±标准差,mmHg)为176±16/79±8,SDH组为167±23/97±7,血压正常对照组为134±14/74±9。正常人群中M和T等位基因的频率(分别为0.69和0.31)在ISH组(分别为0.61和0.39;χ² = 6.0,P < 0.02)和SDH组(分别为0.62和0.38;χ² = 6.0,P < 0.02)中发生了显著变化。TT基因型的存在对ISH(优势比1.9,95%置信区间1.1 - 3.3)和SDH(1.7,1.0 - 3.0)均有预测作用,T等位基因对ISH(1.3,1.0 - 1.7;SDH:1.3,1.0 - 1.7)也有预测作用。

结论

M235→T多态性可能是老年人两种高血压形式的一个标志物。TT基因型是否代表晚年发生高血压的遗传危险因素尚需证实。

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