Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study
Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study
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DOI：
10.1161/01.cir.97.18.1766
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发表时间：
1998-05-12
期刊：
影响因子：
37.8
通讯作者：
Levy, D
中科院分区：
文献类型：
--
作者：
O'Donnell, CJ;Lindpaintner, K;Levy, D
背景——关于血管紧张素转换酶缺失-插入（ACE D/I）多态性与全身性高血压和血压的关系存在争议。我们通过关联分析和连锁分析，在大量基于人群的男性和女性样本中调查了这些关系。方法和结果——研究样本由 Framingham 心脏研究的 3095 名参与者组成。定期检查时测量血压。 ACE D/I 多态性通过聚合酶链式反应测定进行鉴定。在逻辑回归分析中，DD 和 DI 基因型男性高血压的调整后比值比分别为 1.59（95% 置信区间 [CI]，1.13 至 2.23）和 1.18（95% CI，0.87 至 1.62），而 II 基因型（Chi(2) P=.02）。在女性中，DD 和 DI 基因型的调整后优势比分别为 1.00（95% CI，0.70 至 1.44）和 0.78（95% CI，0.56 至 1.09）（P=.14）。在线性回归分析中，ACE DD 基因型与男性舒张压升高相关（年龄调整 P=.03，多变量调整 P=.14），但与女性无关。通过使用 ACE D/I 和附近的人类生长激素基因的微卫星多态性，对 1044 对兄弟姐妹进行数量性状连锁分析，支持 ACE 基因座在影响男性血压方面的作用，但不影响女性血压。结论 - 在我们基于人口的大型样本中，有证据表明 ACE 基因座与男性高血压和舒张压相关，但与男性而非女性舒张压相关。我们的数据支持以下假设：ACE、或附近的基因，是高血压的性别特异性候选基因。有必要在其他大型人群样本中进行验证性研究。
Background-There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses.Methods and Results-The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (Chi(2) P=.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women.Conclusions-In our large, population-based sample, then is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women, Our data support the hypothesis that ACE, or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted.