Heritability of Angiotensin-Converting Enzyme and Angiotensinogen

Abstract —Angiotensinogen (AGT) and angiotensin I–converting enzyme (ACE) are heritable traits, but whether the environmental context influences heritability has not been examined. Known genetic factors explain only a portion of variation in AGT and ACE, and levels of both proteins are influenced by the environment. The African diaspora provides an opportunity to compare these traits in genetically related populations in contrasting environments. As part of a study of the genetics of hypertension, we examined families that included 1449 Nigerians and 1147 African Americans. Body mass index (weight [kg]/height [m] 2 ) was 21 kg/m 2 in Nigeria and 29 kg/m 2 in the United States, which is consistent with a large environmental contrast. AGT was considerably higher among African Americans (1919 versus 1396, P <0.01), whereas ACE was higher in Nigerians (630 versus 517, P <0.01). A household effect was observed among the Nigerian families (spouse correlations 0.30 for AGT, 0.18 for ACE), and correlations among first-degree relatives were large (0.42 to 0.51 and 0.36 to 0.38 for AGT and ACE, respectively). Among African Americans, the familial aggregations of AGT and ACE were very limited, and the familial correlation for AGT was not different from zero. Heritability was 77% for AGT and 67% for ACE in Nigeria and 18% for AGT and ACE in the United States. The familial patterns of body mass index and blood pressure were similar among both family sets. In conclusion, less familial aggregation was observed for AGT and ACE in the United States than in Nigeria, most likely reflecting a greater random individual environmental effect on these traits. Variation in heritability of traits could influence the power of epidemiological studies to identify genetic effects.