The SNP rs9677 of VPAC1 gene is associated with glycolipid control and heart function in female patients with type 2 diabetes: A follow-up study

Nutr Metab Cardiovasc Dis. 2016 Feb;26(2):109-13. doi: 10.1016/j.numecd.2015.10.009. Epub 2015 Oct 30.

Abstract

Background and aims: In a previous study, the single-nucleotide polymorphism (SNP) rs9677, mapped in the 3'-UTR of vasoactive intestinal peptide receptor 1 (VPAC1) gene, was found to be associated with type 2 diabetes (T2D) in Caucasian women. Moreover, the CC genotype correlated with a worse glycolipid profile. The objectives of this study were to confirm this correlation and assess the prevalence of coronary artery disease (CAD) in the previously investigated diabetic women after a follow-up of 4.6 years.

Methods and results: A total of 143 women with T2D, with 53 carrying the CC genotype (age: 71.7 ± 7.4 years, diabetes duration: 17.2 ± 9.9 years) and 90 carrying the CT + TT genotypes (age: 69.4 ± 8.8 years, diabetes duration: 14.3 ± 8.2 years), were followed up for 4.6 ± 1.8 years. At follow-up, the clinical and haematochemical parameters were analysed. Twelve-lead electrocardiography, Doppler echocardiography and the percentage of patients with acute myocardial infarction (AMI) or of those subjected to coronary angioplasty and coronary artery bypass surgery were evaluated. At follow-up, there was no significant difference in terms of the clinical and haematochemical parameters between the two groups. However, despite a significantly increased use of statin therapy, no significant improvement in the LDL cholesterol levels was observed in CC female patients unlike those with CT + TT (P = 0.02). Moreover, the CC female patients presented a significantly higher percentage of echocardiographic abnormalities (P = 0.035), especially left ventricular (LV) diastolic dysfunction (P = 0.04).

Conclusions: The rs9677 CC genotype could be correlated with a reduced response to statin therapy and seems to be involved in diabetes cardiomyopathy in female patients with T2D.

Keywords: Cardiovascular disease; Dyslipidaemia; Female; Type 2 diabetes; Vasoactive intestinal peptide; Vasoactive intestinal peptide receptor 1.

MeSH terms

  • 3' Untranslated Regions
  • Aged
  • Angioplasty, Balloon, Coronary
  • Biomarkers / blood
  • Cholesterol, LDL / blood*
  • Coronary Artery Bypass
  • Coronary Artery Disease / ethnology
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / physiopathology
  • Coronary Artery Disease / therapy
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Angiopathies / ethnology
  • Diabetic Angiopathies / genetics*
  • Diabetic Angiopathies / physiopathology
  • Diabetic Angiopathies / therapy
  • Diabetic Cardiomyopathies / ethnology
  • Diabetic Cardiomyopathies / genetics*
  • Diabetic Cardiomyopathies / physiopathology
  • Diabetic Cardiomyopathies / therapy
  • Dyslipidemias / blood
  • Dyslipidemias / drug therapy
  • Dyslipidemias / ethnology
  • Dyslipidemias / genetics*
  • Echocardiography, Doppler
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Italy / epidemiology
  • Middle Aged
  • Myocardial Infarction / ethnology
  • Myocardial Infarction / genetics
  • Myocardial Infarction / physiopathology
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / genetics*
  • Risk Factors
  • Time Factors
  • Ventricular Dysfunction, Left / ethnology
  • Ventricular Dysfunction, Left / genetics
  • Ventricular Dysfunction, Left / physiopathology
  • White People / genetics

Substances

  • 3' Untranslated Regions
  • Biomarkers
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Receptors, Vasoactive Intestinal Polypeptide, Type I
  • VIPR1 protein, human