Genetic studies of the renin-angiotensin system in arterial hypertension associated with non-insulin-dependent diabetes mellitus

Abstract

To determine whether angiotensinogen (AGT) and angiotensin II type 1 (AT1) receptor genes contribute to the development of arterial hypertension in members of French Caucasian families and in subjects with hypertension associated with non-insulin-dependent diabetes mellitus (NIDDM). Sibpair linkage analyses were performed with microsatellites near the AGT and AT1 receptor genes in 179 hypertensive sibpairs from 69 NIDDM kindreds. In addition, population/association studies were performed with the M235T and T174M polymorphisms of the AGT gene, and the A1166C polymorphism of the AT1 receptor gene. No evidence for linkage between the AGT and AT1 receptor loci and hypertension was observed. In addition, the distributions of genotypes of AGT and AT1 receptor gene polymorphisms did not differ significantly among a group of unrelated individuals with both hypertension and NIDDM (n = 188) and three groups of unrelated control subjects with NIDDM (n = 117), hypertension (n = 75) or none of these conditions (n = 125). These results suggest that the AGT and AT1 receptor genes are not major genetic determinants of hypertension associated with NIDDM in this population, although we can not exclude the possibility that these loci make a minor contribution in a polygenic context.