T+31C Polymorphism of Angiotensinogen Gene and Essential Hypertension

Abstract

A common variant at codon 235 of the angiotensinogen gene with methionine to threonine amino acid substitution ( AGT M235T ) has been reported as a genetic risk for essential hypertension. However, the frequency of AGT T235 was heterogeneous among races, and a positive association between AGT M235T and hypertension was not settled. To examine the association in a general population of Japanese (n=4013), we introduced the TaqMan polymerase chain reaction method and examined the relation between hypertension and T+31C polymorphism, which was in absolute linkage disequilibrium with AGT M235T. The C+31 allele of AGT was significantly associated with the positive family history of hypertension (FH) but not with the presence of hypertension or blood pressure. The subjects with CC tended to have hypertensive relatives, especially a hypertensive father or siblings, and its statistical significance was stronger in men. Adjustment of confounding factor did not alter the results of simple association study, suggesting that this positive association with FH is independent and significant. Our findings revealed that the TaqMan polymerase chain reaction method is a powerful tool for genetic association study with a large number of subjects and that AGT T+31C is significantly associated with paternal FH.