Association of (-)786T-C mutation of endothelial nitric oxide synthase gene with insulin resistance.
OBJECTIVE
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.


METHODS
Genotypes of both Glu298Asp and (-)786T-C mutation were examined by the PCR-RFLP method. Plasma nitrate and nitrite concentrations were also measured.


RESULTS
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.


CONCLUSIONS
The (-)786T-C mutation of the eNOS gene is associated with insulin resistance in both Japanese non-diabetic subjects and Type II diabetic patients.
Ohtoshi
K
K
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita City, Japan.
Yamasaki
Y
Y
Gorogawa
S
S
Hayaishi-Okano
R
R
Node
K
K
Matsuhisa
M
M
Kajimoto
Y
Y
Hori
M
M
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D001794:Blood Pressure; D003562:Cytidine; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D013941:Thymine
D017931:DNA Primers; D009566:Nitrates; D009573:Nitrites; D003562:Cytidine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D013941:Thymine