Association of -786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance

• Published in: Diabetologia Vol. 45; no. 11; pp. 1594 - 1601
• Main Authors: OHTOSHI, K, YAMASAKI, Y, GOROGAWA, S, HAYAISHI-OKANO, R, NODE, K, MATSUHISA, M, KAJIMOTO, Y, HORI, M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-11-2002; Springer Nature B.V
• Subjects: Adult; Aged; Asian Continental Ancestry Group - genetics; Base Sequence; Biological and medical sciences; Blood Pressure; Cytidine; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; DNA Primers; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exons; Female; Gene Frequency; Humans; Insulin resistance; Insulin Resistance - genetics; Japan; Male; Medical sciences; Middle Aged; Nitrates - blood; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type III; Nitrites - blood; Point Mutation; Polymorphism, Single Nucleotide; Reference Values; Thymine; Japan; Endocrinopathy; Human; Enzyme; Diabetes mellitus; glucose infusion rate; homeostasis model assessment of insulin resistance insulin resistance; Insulin; Nitric-oxide synthase; Target tissue resistance; intima-media thickness; Endothelial nitric oxide synthase; Association; Gene; Oxidoreductases; Mutation; Polymorphism
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-002-0922-6

Endothelial derived nitric oxide synthase ( eNOS) gene polymorphisms affect eNOS activity and are associated with abnormal vasomotility and impaired local blood flow. A decrease in local blood flow has been reported to cause insulin resistance. The aim of this study was to examine a possible association of two eNOS polymorphisms, Glu298Asp (G894T) in exon 7 and (-)786T-C mutation with insulin resistance.
Genotypes of both Glu298Asp and (-)786T-C mutation were examined by the PCR-RFLP method. Plasma nitrate and nitrite concentrations were also measured.
The allele frequencies of both polymorphisms showed no considerable differences in 233 non-diabetic subjects and 301 patients with Type II (non-insulin-dependent) diabetes mellitus. Non-diabetic subjects with the (-)786C allele had (p<0.05) higher fasting plasma insulin and homeostasis model assessment of insulin resistance than those with the (-)786T/ (-)786T genotype. Diabetic subjects with (-)786C allele showed higher HbA(1c) than those with the (-)786T/(-)786T genotype. A euglycaemic hyperinsulinemic clamp study done on 71 of the 301 patients showed a lower glucose infusion rate in diabetic patients with the (-)786C allele than those without it. In diabetic patients with the (-)786C allele, plasma nitrate and nitrite concentrations were lower than in subjects without it (p=0.026). No differences were observed between mutant carriers of Glu298Asp and non-carriers among both non-diabetic subjects and Type II diabetic patients.
The (-)786T-C mutation of the eNOS gene is associated with insulin resistance in both Japanese non-diabetic subjects and Type II diabetic patients.