Polymorphism in exon 7 of the endothelial nitric oxide synthase gene is associated with low incidence of microvascular damage in type 1 diabetic neuropathy

Microvascular complications associated with type 1 diabetes mellitus (T1DM) are caused in part by endothelial dysfunction. We aimed to determine the association between polymorphisms in endothelial nitric oxide synthase (eNOS) gene (894G>T, 4ab) and T1DM-associated microvascular disorders, and the roles of nitrite/nitrate products (NOx) and low molecular weight-AGEs (LMW-AGEs) levels in this relationship. We carried out a case-control study (328 subjects) and determined genotypes by PCR. The rare-type TT of eNOS 894G>T was significantly overrepresented in patients without microvascular disorders as compared with control (OR=3.64; 95% C.I.=1.02–12.73; P=0.039). The prevalence of neuropathy was high among 894GG homozygotes (OR=0.5; 95% C.I.=0.29–0.86; P=0.012) who had high levels of triglycerides, elevated systolic BP, increased NOx, and LMW-AGEs. Decreased NOx levels were associated with 894TT genotype (beta=−0.65; P=0.043) in diabetic patients prone to microvascular complications. Multiple regression analysis indicated a negative correlation between eNOS 894G>T and diabetic neuropathy (P=0.025). The distribution of eNOS 4aa genotype was high (P=0.042) in patients with T1DM; however, it does not represent a risk factor for neuropathy. The overrepresentation of eNOS 894TT genotype in diabetic patients is associated with low risk for neuropathy. Decreased NOx and LMW-AGEs levels and lower lipid profile are the main features of patients carrying the eNOS 894T allele. These data suggest that the eNOS 894TT genotype may play a protective role by preventing microvascular disorders.