title: The type 2 diabetes and insulin-resistance locus near IRS1 is a determinant of HDL cholesterol and triglycerides levels among diabetic subjects.
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.
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, MA, United States.
authors.forename: Rajani
authors.initials: R
authors.lastname: Sharma
authors.forename: Sabrina
authors.initials: S
authors.lastname: Prudente
authors.forename: Francesco
authors.initials: F
authors.lastname: Andreozzi
authors.forename: Christine
authors.initials: C
authors.lastname: Powers
authors.forename: Gaia
authors.initials: G
authors.lastname: Mannino
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bacci
authors.forename: Ernest V
authors.initials: EV
authors.lastname: Gervino
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hauser
authors.forename: Elena
authors.initials: E
authors.lastname: Succurro
authors.forename: Luana
authors.initials: L
authors.lastname: Mercuri
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Goheen
authors.forename: Hetal
authors.initials: H
authors.lastname: Shah
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trischitta
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Doria
mesh_terms: D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D001900:Boston; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D007558:Italy; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D014280:Triglycerides