T(−786)→C polymorphism of the endothelial nitric oxide synthase gene is associated with insulin resistance in patients with ischemic or non ischemic cardiomyopathy
Open accessAbstract
BACKGROUND: Insulin resistance (IR) and endothelial dysfunction are frequently associated in cardiac disease. The T(-786)→C variant in the promoter region of the endothelial nitric oxide synthase (eNOS) gene has been associated with IR in both non-diabetic and diabetic subjects. Aim of the study was to assess the reciprocal relationships between T(-786)→C eNOS polymorphism and IR in ischemic and non-ischemic cardiomyopathy. METHOD: A group of 132 patients (108 males, median age 65 years) with global left ventricular (LV) dysfunction secondary to ischemic or non-ischemic heart disease was enrolled. Genotyping of T(-786)→C eNOS gene promoter, fasting glucose, insulin, and insulin resistance (defined as HOMA-IR index > 2.5) were determined in all patients. RESULTS: Genotyping analysis yielded 37 patients homozygous for the T allele (TT), 70 heterozygotes (TC) and 25 homozygous for C (CC). Patients with CC genotype had significantly higher systemic arterial pressure, blood glucose, plasma insulin and HOMA index levels than TT. At multivariate logistic analysis, the history of hypertension and the genotype were the only predictors of IR. In particular, CC genotype increased the risk of IR (CI% 1.4-15.0, p < 0.01) 4.5-fold. The only parameter independently associated with the extent of LV dysfunction and the presence of heart failure (HF) was the HOMA index (2.4 CI% 1.1-5.6, p < 0.04). CONCLUSIONS: T(-786)→C eNOS polymorphism was the major independent determinant of IR in a population of patients with ischemic and non-ischemic cardiomyopathy. The results suggest that a condition of primitive eNOS lower expression can predispose to an impairment of glucose homeostasis, which in turn is able to affect the severity of heart disease.
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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 [320]
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Self-citation
- Authors
- Vecoli, C., Andreassi, M. G., Liga, R., Colombo, M. G., Coceani, M., Carpeggiani, C., L’Abbate, A., & Neglia, D.
- Affiliations
- Istituto di Fisiologia Clinica (IT)
- Scuola Superiore Sant'Anna (IT)
- Corresponding author
- Vecoli, Cecilia
- ORCID
- Venue
- BMC Medical Genetics
- Published
- 2012-10-02
- Volume
- 13
- Issue
- 1
- Pages
- 92-92
- ISSN
- 1471-2350 (ISSN-L)
- PMC
- PMC3495192
- OpenAlex
- W2062715868
- Cited by
- 22
- References
- 22
- Citations by year
- 2024: 3 · 2022: 2 · 2020: 2 · 2018: 1 · 2017: 5 · 2016: 1 · 2014: 6 · 2013: 2
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Medical Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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, ischemic cardiomyopathy, non-ischemic cardiomyopathy, left ventricular dysfunction, hypertension, heart failure, glucose homeostasis, endothelial dysfunction, HOMA-IR
- MeSH terms
- Aged, Alleles, Blood Glucose, Blood Pressure, Female, Genotype, Heart Failure, Heterozygote, Homozygote, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Cardiomyopathies, Predictive Value of Tests, Promoter Regions, Genetic, Risk Factors, Logistic Models, Ventricular Dysfunction, Left, Polymorphism, Single Nucleotide, Nitric Oxide Synthase Type III
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