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Cardiovascular disease and diabetic nephropahty account for much of the morbidity and mortality associated with diabetes mellitus. Genotypic abnormalities of the reninangiotensin system have been suggested as a risk factor for the development of diabetic complications. We studied the relationship between an insertion(I)/deletion(D) polymorphism in angiotensin converting enzyme (ACE) gene in non-insulin dependent diabetes mellitus (NIDDM) patients with various diabetic complications
We examined 159 patients (Mean age 58.1 ±12.1 years) with NIDDM of more than 3 years duration. (Mean duration of diabetes; 11.7+8 years). As control we took 44 healthy volunteers (Mean age 55.3+9.9 years). The 1/D polymorphism was analyzed with PCR technique and alleles were visualized on %2 agarose gels after ethidium staining. Distribution of genotypes was not significantly different NIDDM patients with and without nephropathy , hypertension, retinopathy, neuropathy. The DD genotype was found to be related with peripheral arterial diseases (P=0.05). ID genotype was related with ischemic heart disease (P=0.03) and cardiomyopathy (P=0.05). No significant gender difference was found between II/ID/DD genotypes and I/D alleles. Serum glucose (P=0.02) and HbAlc (p=0.005) values were significantly high in II genotyped patients. No genotype correlation was found between diabetes and complications in relatives of the patients (P>0.05).
In conclusion there is no significant association between DD/ID/ll genotypes of ACE gene in NIDDM patients with various degrees of diabetic nephropathy (P>0.05). Only patients with diabetic nephropathy who were on renal replacement therapy had D allele more than other diabetic patients and control subjects. Though there is no correlation with diabetic nephropathy ACE gene polymorphism DD and ID genotypes can be a notable genetic marker for cardiovascular and peripheral arterial disease. Follow-up studies is needed to achieve a better understanding of the role of candidate gene polymorphisms on the development of complications of NIDDM