Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension

Even if the importance of angiotensinogen (AGT) gene has been known in gene targeting animals and humans genetic studies, its precise mechanism and th e interaction among AGT gene variants, plasma AGT concentration and risk fo r hypertension remain uncertain. We examined whether AGT gene variants pred ispose to hypertension via an increase of plasma AGT concentration. Plasma AGT concentration was estimated from plasma angiotensin I which was cleaved by an excess amount of human renin and measured by RTA. Using 9 AGT gene v ariants which included new polymorphisms (G-152A and T+31C), we examined th e association with hypertension and with plasma concentration by a case-con trol study. Haplotype analysis revealed that G-6A, T+31C and M235T polymorp hisms were in absolute linkage disequilibrium and were associated with hype rtension but not with plasma AGT level. On the other hand, -1074t;T235 hapl otype was associated with an increase of AGT level but not with hypertensio n. In the haplotype analysis, only H3 haplotype frequency, which contained G-6, T+31 and M235 alleles, was significantly increased in normotensive sub jects, suggesting that this haplotype is associated with a hypotensive effe ct. According to combined haplotype analysis of diallele and microsatellite markers, it remains a possibility that M235T, T+31C, G-6A, A-20C and G-107 4T polymorphisms may play an important role in increased risk for essential hypertension. Our results suggest that the positive association between AG T polymorphism and hypertension is not simply explained by an increase of p lasma AGT concentration. (C) 2000 Elsevier Science Inc. All rights reserved .