The type 2 diabetes and insulin-resistance locus near IRS1 is a determinant of HDL cholesterol and triglycerides levels among diabetic subjects

Atherosclerosis. 2011 May;216(1):157-60. doi: 10.1016/j.atherosclerosis.2011.01.022. Epub 2011 Jan 26.

Abstract

Objective: SNP rs2943641 near the insulin receptor substrate 1 (IRS1) gene has been found to be associated with type 2 diabetes (T2D) and insulin-resistance in genome-wide association studies. We investigated whether this SNP is associated with cardiovascular risk factors and coronary artery disease (CAD) among diabetic individuals.

Methods: SNP rs2943641 was typed in 2133 White T2D subjects and tested for association with BMI, serum HDL cholesterol and triglycerides, hypertension history, and CAD risk.

Results: HDL cholesterol decreased by 1mg/dl (p = 0.004) and serum triglycerides increased by 6 mg/dl (p = 0.016) for each copy of the insulin-resistance allele. Despite these effects, no association was found with increased CAD risk (OR = 1.00, 95% CI 0.88-1.13).

Conclusions: The insulin-resistance and T2D locus near the IRS1 gene is a determinant of lower HDL cholesterol among T2D subjects. However, this effect is small and does not translate into a detectable increase in CAD risk in this population.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Body Mass Index
  • Boston
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / physiopathology
  • Case-Control Studies
  • Cholesterol, HDL / blood*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / physiopathology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension / genetics
  • Insulin Receptor Substrate Proteins / genetics*
  • Insulin Resistance / genetics*
  • Italy
  • Logistic Models
  • Male
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Triglycerides / blood*

Substances

  • Biomarkers
  • Cholesterol, HDL
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Triglycerides