Angiotensin-converting enzyme gene polymorphism and a genetic predisposition to diabetic nephropathy in insulin-dependent diabetes mellitus

Insertion/deletion (ID) polymorphism of angiotensin I converting enzyme (ACE) as a potential marker of genetic susceptibility to diabetic nephropathy (DN) is studied in 45 insulin-dependent diabetic patients and 168 healthy subjects from the general Moscow population. Fourteen proteinuric patients with relatively short diabetes duration (< 15 years) and 31 patients with a longer diabetes duration (>20 years) without clinical signs of DN were the “case” (DN+) and control (DN-) groups, respectively. The DN+ group virtually did not differ from healthy subjects in the ID/ACE allele and genotype distribution, whereas in the DN- and healthy controls and, more so, in the DN+ and DN- groups the incidence of this polymorphic marker differed significantly, and hence, it can be considered as a genetic risk factor for DN. Allele I had a dose-dependent protective effect with regard to DN (maximal in the carriers of homozygotic genotype II). Such non-genetic risk factors as glycemic control, diastolic blood pressure, and sex of patients interfere with ID/ACE polymorphism and contribute to susceptibility to DN in a synergistic or antagonistic manner. Use of the “extreme” variants of DN phenotype helped decrease the masking effect of non-genetic risk factors and detect the genetic component in the etiology and pathogenesis of this multifactorial angiopathy.

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