Risk of developing diabetic nephropathy is not associated with synergism between the angiotensin II (type 1) receptor C-1166 allele and poor glycaemic control

Background. It has recently been reported that the risk of developing nephr opathy in patients with insulin dependent (type 1)diabetes mellitus is stro ngly associated with synergism between poor glycaemic control and carriage of the hypertension associated angiotensin II (type 1) receptor C-1166 alle le. The same report also revealed an increase in risk of nephropathy in dia betic patients carrying a specific angiotensin II (type 1) receptor haploty pe, i.e. C-1166/140-bp microsatellite allele (major allele). Methods. In order to replicate these findings we performed PCR-based genoty ping for the A(1166)-->C DNA polymorphism and the CA repeat at the 3' end o f the angiotensin II (type 1) receptor gene employing validated groups of t ype 1 diabetic patients with (cases, n = 95) and without (controls, n = 97) nephropathy. HbA(1) values above the median (10.5) were used as an index o f poor glycaemic control. Results. The risk of nephropathy in carriers of the C-1166 allele with HbA( 1) > 10.5 was 2.1 (95% CI 0.8-5.2) compared to 1.1 (95% CI 0.4-2.6) for non -carriers of the C-1166 allele; however, these odds ratios were not signifi cantly different. No difference in the frequency of the high-risk haplotype was found in cases compared to controls (12.4 vs 11.5%; chi(2) = 0.01, P = 0.938 with 1 df). Conclusions. The results of this study do not support previous findings tha t the risk of diabetic nephropathy is associated with synergism between poo r glycaemic control and carriage of the C-1166 allele or inheritance of the C-1166/major microsatellite haplotype.