(Hypertension. 1996;27:1134-1139.)
© 1996 American Heart Association, Inc.
Articles |
Angiotensinogen Polymorphism M235T, Hypertension, and Nephropathy in Insulin-Dependent Diabetes
From the Section on Epidemiology and Genetics, Research Division, Joslin Diabetes Center, and the Department of Medicine, Harvard Medical School, Boston, Mass.
Correspondence to Andrzej S. Krolewski, MD, PhD, Section on Epidemiology and Genetics, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215.
Abstract The allele 235T (a threonine in place of a
methionine at position 235) of angiotensinogen has been
found to be associated with a predisposition to essential hypertension.
We investigated whether this allele also confers increased
susceptibility to nephropathy in patients with
insulin-dependent diabetes mellitus (IDDM). A group of 380 patients
who had had IDDM for 15 to 20 years were genotyped at the
angiotensinogen 235 locus. Included were 75 patients with
normoalbuminuria (albumin excretion rate <30
µg/min), two series of patients with microalbuminuria
(n=30 and n=136), and two series with overt proteinuria (n=41 and
n=98). Allele 235T frequency was higher among cases with
microalbuminuria (0.41 in the two series combined) or
overt proteinuria (0.40) than in the normoalbuminuria
group (0.36). However, this difference was not statistically
significant with this sample size (
2=1.2,
P=NS with 2 df). Under a recessive model,
allele 235T homozygotes had a 1.6-fold risk of developing
nephropathy relative to carriers of other
genotypes, 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 stratification by degree of glycemic control. With respect to the
hypertension in these IDDM patients, no association with allele
235T was found. Allele 235T frequencies in normotensive and
hypertensive individuals were 0.363 and 0.353, respectively,
among normoalbuminuric IDDM individuals
(2=0.01, P=NS) and 0.411 and 0.414
among microalbuminuric IDDM subjects
(2=0.0, P=NS). We conclude that the
angiotensinogen polymorphism M235T might influence
susceptibility to nephropathy in insulin-dependent
diabetes, but its effect, if any, is rather small and independent of
hypertension.
Key Words: genetics • insulin-dependent diabetes • nephropathy • angiotensinogen
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