ANGIOTENSINOGEN POLYMORPHISM M235T, HYPERTENSION, AND NEPHROPATHY IN INSULIN-DEPENDENT DIABETES

The allele 235T (a threonine in place of a methionine at position 235) of angiotensinogen has been found to be associated with a predisposit ion to essential hypertension. We investigated whether this allele als o confers increased susceptibility to nephropathy in patients with ins ulin-dependent diabetes mellitus (IDDM). A group of 380 patients who h ad had IDDM for 15 to 20 years were genotyped at the angiotensinogen 2 35 locus. Included were 75 patients with normoalbuminuria (albumin exc retion rate <30 mu g/min), two series of patients with microalbuminuri a (n=30 and n=136), and two series with overt proteinuria (n=41 and n= 98). Allele 235T frequency was higher among cases with microalbuminuri a (0.41 in the two series combined) or overt proteinuria (0.40) than i n the normoalbuminuria group (0.36). However, this difference was not statistically significant with this sample size (chi(2)=1.2, P=NS with 2 df). Under a recessive model, allele 235T homozygotes had a 1.6-fol d risk of developing nephropathy relative to carriers of other genotyp es, but this value was not significantly different from 1 (95% CI=0.8 to 3.5). The strength of the association did not improve after stratif ication by degree of glycemic control. With respect to the hypertensio n in these IDDM patients, no association with allele 235T was found. A llele 235T frequencies in normotensive and hypertensive individuals we re 0.363 and 0.353, respectively, among normoalbuminuric IDDM individu als (chi(2)=0.01, P=NS) and 0.411 and 0.414 among microalbuminuric IDD M subjects (chi(2)=0.0, P=NS). We conclude that the angiotensinogen po lymorphism M235T might influence susceptibility to nephropathy in insu lin-dependent diabetes, but its effect, if any, is rather small and in dependent of hypertension.