Angiotensinogen gene polymorphisms M235T/T174M: no excess transmission to hypertensive Chinese

The gene encoding angiotensinogen (AGT) has been widely studied as a candidate gene for hypertension. Most studies to date have relied on case-control analysis to test for an excess of AGT variants among hypertensive cases compared with normotensive controls. However, with this design, nothing guarantees that a positive finding is due to actual allelic association as opposed to an inappropriate control population. To avoid this difficulty in our study of essential hypertension in Anqing, China, we tested AGT variants using the transmission/disequilibrium test, a procedure that bypasses the need for a control sample by testing for excessive transmission of a genetic variant from parents heterozygous for that variant. We analyzed two AGT polymorphisms, M235T and T174M, which have been associated with essential hypertension in whites and Japanese, using data on 335 hypertensive subjects from 315 nuclear families and their parents. Except in the group of subjects younger than 25 years, M235 and T174 were the more frequently transmitted alleles. We found that 194 parents heterozygous for M235T transmitted M235 106 times (P=0.22) and that 102 parents heterozygous for T174M transmitted T174 60 times (P=0.09). Stratifying offspring by gender, M235 and T174 were transmitted 60 of 106 times (P=0.21) and 44 of 75 times (P=0.17), respectively, in men, and 46 of 88 times (P=0.75) and 16 of 27 times (P=0.44), respectively, in women. Our results were also negative in all age groups and for the affected offspring with blood pressure values >/=160/95 mm Hg. Thus, this study provides no evidence that either allele of M235T or T174M contributes to hypertension in this Chinese population.