Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Am J Hypertens. 2012 Feb;25(2):209-15. doi: 10.1038/ajh.2011.182. Epub 2011 Oct 13.
The insertion/deletion (I/D) variant (rs4646994) of the angiotensin I-converting enzyme (ACE) gene is one of the most studied polymorphisms in relation to blood pressure and essential hypertension in humans. The evidence to date, however, on an association of this variant with blood pressure-related outcomes has been inconclusive.
We examined 5,561 participants of the Third National Health and Nutrition Examination Survey (NHANES III), a population-based and nationally representative survey of the United States, who were ≥20 years of age and who self-identified as non-Hispanic white, non-Hispanic black, or Mexican American. Within each race/ethnicity, we assessed genetic associations of the I/D variant with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension, as well as genotype-sex interactions, in four genetic models (additive, dominant, recessive, and codominant).
The frequency of the I/D variant differed significantly by race/ethnicity (P = 0.001). Among non-Hispanic blacks, the D allele was significantly associated (P < 0.05) with increased SBP in additive and dominant covariate-adjusted models and was also associated with increased DBP in dominant models when participants taking ACE inhibitors were excluded from the analyses. No other significant associations were observed in any race/ethnic group. Significant genotype-sex interactions were detected among Mexican Americans, for whom positive associations with SBP and hypertension were seen among females, but not males.
This study gives limited support for association of the ACE I/D variant with blood pressure and for sex-specific effects among particular race/ethnic groups, though we cannot rule out the role of genetic or environmental interactions.
血管紧张素转换酶（ACE）基因的插入/缺失（I/D）变体（rs4646994）是与人类血压和原发性高血压关系最密切的研究最多的多态性之一。然而，迄今为止，关于该变体与血压相关结果的关联的证据尚无定论。
我们检查了第三次全国健康和营养检查调查（NHANES III）的 5561 名参与者，这是一项针对美国人口的基于人群的全国代表性调查，参与者年龄≥20 岁，自认为是非西班牙裔白人，非西班牙裔黑人或墨西哥裔美国人。在每个种族/民族中，我们评估了 I/D 变体与收缩压（SBP），舒张压（DBP）和高血压的遗传关联，以及四种遗传模型（加性，显性，隐性和共显性）中的基因型性别相互作用。
I/D 变体的频率在种族/民族之间存在显着差异（P = 0.001）。在非西班牙裔黑人中，D 等位基因在加性和显性协变量调整模型中与 SBP 增加显着相关（P <0.05），当从分析中排除服用 ACE 抑制剂的参与者时，D 等位基因也与 DBP 增加相关在显性模型中。在任何种族/民族群体中均未观察到其他显着关联。在墨西哥裔美国人中检测到显着的基因型性别相互作用，其中女性与 SBP 和高血压呈正相关，但男性则无。
这项研究为 ACE I/D 变体与血压之间的关联以及特定种族/民族群体中性别特异性效应提供了有限的支持，尽管我们不能排除遗传或环境相互作用的作用。
