ANGIOTENSIN-II TYPE-1 RECEPTOR GENE POLYMORPHISMS IN HUMAN ESSENTIAL-HYPERTENSION

We conducted the present study to determine whether the angiotensin II type I receptor (AT(1)) gene might be implicated in human essential hypertension by using case-control and linkage studies. The entire coding and 3' untranslated regions of the AT(1) receptor gene (2.2 kb) were amplified by polymerase chain reaction and submitted to single-strand conformation polymorphism in 60 hypertensive subjects with a familial susceptibility. We identified five polymorphisms (T-573-->C, A(1062)-->G, A(1166)-->C, G(1517)-->T, and A(1878)-->G). However, no mutations that alter the encoded amino acid sequence were detected. A case-control study performed on white hypertensive (n=206; blood pressure, 168+/-16/103+/-9 mm Hg) and normotensive (n=298; blood pressure, 122+/-10/75+/-9 mm Hg) subjects using three of five polymorphisms showed a significant increase in allelic frequency of C-1166 in hypertensive subjects (0.36 versus 0.28 for normotensive subjects, chi(2)=6.8, P<.01). Frequencies for the alleles of the other two polymorphisms (T-573-->C, A(1878)-->G) were similar in both groups. We performed a linkage study using the affected sib pair method and a highly polymorphic marker of the AT(1) receptor gene. There was no evidence for linkage in 267 sib pairs analyzed from 138 pedigrees. These findings would be compatible with a common variant of the AT(1) receptor imparting a small effect on blood pressure; further studies will be needed to address this possibility.