Cited by 71Nitric Oxide and Endothelin EffectsDiabetes, Cardiovascular Risks, and LipoproteinsGenetic Associations and Epidemiology

Association of (−)786T–C mutation of endothelial nitric oxide synthase gene with insulin resistance

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K., Ohtoshi, Y., Yamasaki, S., Gorogawa, R., Hayaishi-Okano, K., Node, M., Matsuhisa, Y., Kajimoto, M., Hori·2002·Diabetologia

Abstract

Aims/hypothesis 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/interpretation The (-)786T-C mutation of the eNOS gene is associated with insulin resistance in both Japanese non-diabetic subjects and Type II diabetic patients.

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  • Several studies have associated a T(−786)C variant of the NOS3 gene with insulin resistance.

    “Most notably, several studies have associated a T(−786)C variant of the NOS3 gene with insulin resistance [318-320].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [318]

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Authors
K., O., Y., Y., S., G., R., H.-O., K., N., M., M., Y., K., & M., H.
Venue
Diabetologia
Published
2002-11-01
Volume
45
Issue
11
Pages
1594-1601
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
OpenAlex
W1983844941
Cited by
71
References
48
Citations by year
2024: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 3 · 2016: 2 · 2014: 4 · 2013: 3 · 2012: 7
FWCI
2.39
Type
journal article
Language
en
Open access
Locations
  • Diabetologia (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
endothelial nitric oxide synthase, insulin resistance, type 2 diabetes, Glu298Asp polymorphism, nitric oxide, HbA1c, glucose infusion rate, Japanese population
MeSH terms
Adult, Aged, Base Sequence, Blood Pressure, Cytidine, Diabetes Mellitus, Type 2, Exons, Female, Gene Frequency, Humans, Insulin Resistance, Japan, Male, Middle Aged, Nitrates, Nitrites, Reference Values, Thymine, Point Mutation, DNA Primers, Nitric Oxide Synthase, Polymorphism, Single Nucleotide, Asian People, Nitric Oxide Synthase Type III

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