Nitric oxide synthase gene polymorphisms and nephropathy in Asians with type 2 diabetes

Objective: Recent studies on Caucasians have reported an association between diabetic microvascular complications and polymorphisms in the inducible nitric oxide synthase (NOS) gene. In view of the differences in the pattern of diabetic complications in Asians, we studied these NOS polymorphisms in Asians with Type 2 diabetes who do and those who do not have nephropathy. Methods: Two hundred fifty-eight Asians who have had Type 2 diabetes for at least 10 years, with overt nephropathy or with normoalbuminuria, were genotyped for the (AAAT)(n) and (CCTTT)(n) polymorphisms in the promoter region of the NOS gene. A subanalysis was made of the findings from the three ethnic groups (Chinese, Malays, and Indians). Results: The (AAAT)(3) polymorphism, which is the most common allele in Caucasians, was completely absent in our entire cohort of 258 Asian diabetics. The (AAAT)(4) polymorphism was the commonest, with a frequency of 0.984 as compared with 0.2 in Caucasians. We also found previously unreported alleles: (AAAT)(5) in 6 patients and (AAAT)(6) in 1 patient. There was no statistically significant association with nephropathy, in view of the highly skewed distribution of the alleles. However, the higher repeats (AAAT)(5) and (AAAT)(6) were found in the patients with a very rapid onset of severe nephropathy. The (CCTTT)(n) polymorphism also showed significant differences in allele distribution between the Asian and the Caucasian and African populations (P=.001). However, there was also no significant association with nephropathy and no significant difference in the ethnic distribution of alleles. Conclusions: We have identified significant differences in the (AAAT)(n) and (CCTTT)(n) polymorphisms in Asian diabetics. We have shown that there are significant differences in the overall allele distribution between the Asian and the Caucasian and African populations. However, our study did not demonstrate an association between NOS gene polymorphisms and diabetic nephropathy. (c) 2006 Elsevier Inc. All rights reserved.