A polymorphism of the angiotensinogen gene associated with variation in blood pressure in a genetic isolate.

BACKGROUND The Hutterite Brethren are a genetic isolate characterized by high indices of relatedness and a communal agrarian lifestyle. We hypothesized that variation of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes would be associated with variation in resting blood pressure in this group. We also hypothesized that the association would depend on the sex of the subjects. METHODS AND RESULTS In 741 Hutterites, we measured blood pressure in quadruplicate and analyzed DNA for genotypes of an insertion/deletion (I/D) polymorphism of ACE and of two protein polymorphisms of AGT, namely, M235T and T174M. We tested for association between variation in systolic and diastolic blood pressures and genotypic class. We observed that genotypes of AGT codon 174 were significantly associated with variation in systolic blood pressure. We also tested for an interaction between the AGT genotype and sex. We observed that genotypes of AGT codon 174 were significantly associated with variation in systolic blood pressure only in men. The AGT codon 174 polymorphism accounted for 3.1% of the total variation in systolic blood pressure in men. CONCLUSIONS The association of AGT variation with resting blood pressure in men is consistent with the existence of important structural elements within, flanking, or proximal to the AGT gene, whose functional impact might be related to differences in sex.