GENETIC-VARIANTS OF THE RENIN-ANGIOTENSIN SYSTEM, DIABETIC NEPHROPATHY AND HYPERTENSION

Recent studies have suggested an association between a deletion (D) va riant of the angiotensin-converting-enzyme (ACE) gene and diabetic nep hropathy. However, this finding has not been confirmed by all investig ators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for t he development and progression of diabetic nephropathy. The objective of our study was therefore to examine the relationship between these g enetic variants of the renin-angiotensin system and diabetic nephropat hy and hypertension, respectively, in a large (n = 661) group of Cauca sian patients with insulin-dependent (n = 360) or non-insulin-dependen t (n = 301) diabetes mellitus. The study had a power of 0.8 to detect a doubling of risk of nephropathy or hypertension in patients with the ACE-DD or AGT-235TT genotype, respectively. Allelic frequencies of th e ACE-D and AGT-235T alleles were similar between patients with and wi thout nephropathy in either type of diabetes, and accordingly, there w as no significant association between diabetic nephropathy and the ACE or AGT genotype. Likewise, there was no significant association betwe en the ACE or AGT genotype and hypertension. Thus, our data, in this l arge and ethnically homogeneous group of patients, do not support the hypothesis that these genetic variants of the renin-angiotensin system are strongly associated with either nephropathy or hypertension in pa tients with insulin-dependent or non-insulin-dependent diabetes mellit us. These genetic markers are therefore unlikely to serve as clinicall y useful predictors of either nephropathy or hypertension in Caucasian patients with diabetes.