title: T(-786)→C polymorphism of the endothelial nitric oxide synthase gene is associated with insulin resistance in patients with ischemic or non ischemic cardiomyopathy.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: CNR, Institute of Clinical Physiology, Pisa, Italy. vecoli@ifc.cnr.it
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vecoli
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Liga
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Colombo
authors.forename: Michele
authors.initials: M
authors.lastname: Coceani
authors.forename: Clara
authors.initials: C
authors.lastname: Carpeggiani
authors.forename: Antonio
authors.initials: A
authors.lastname: L'Abbate
authors.forename: Danilo
authors.initials: D
authors.lastname: Neglia
mesh_terms: D000368:Aged; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000235:genetics*; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000150:complications / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007328:Insulin; D052250:Nitric Oxide Synthase Type III