title: Gly1057Asp polymorphism of insulin receptor substrate-2 is associated with coronary artery disease in the Taiwanese population.
abstract: BACKGROUND
  Gly1057Asp polymorphism in insulin receptor substrate (IRS)-2 is related to insulin resistance and diabetes mellitus (DM), which both contribute to the pathogenesis of coronary artery disease (CAD). Hence, we hypothesize that Gly1057Asp polymorphism in IRS-2 is associated with CAD.
  
  
  METHODS
  Patients receiving elective coronary angiography were enrolled. Significant stenosis is defined as a luminal diameter stenosis greater than 50%. Patients without significant stenosis were defined as group A, and those with significant stenosis in at least one major coronary artery were defined as group B. Genotypes were determined by polymerase chain reaction/restriction fragment length polymorphism. Chi-square test and multivariate logistic regression were used to evaluate the relationship between Gly1057Asp polymorphism in IRS-2 and CAD. The homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated as a representative of insulin resistance. Multiple linear regression was used to analyze the association between Gly1057Asp polymorphism in IRS-2 and the HOMA-IR index.
  
  
  RESULTS
  There were 170 patients in group A and 284 patients in group B. The Gly allele frequencies were 54.7% for group A and 60.9% for group B (p = 0.077). The Gly/Gly + Gly/Asp genotype frequency was 74.1% for group A and 84.9% for group B (p = 0.007). After adjustments for conventional risk factors in multivariate logistic regression, the odds ratio for CAD in patients with the Gly/Gly + Gly/Asp genotype was 2.008 [95% confidence interval (95% CI) = 1.210-3.332, p = 0.007], using patients with the Asp/Asp genotype as a reference group. The concurrence of Gly1057Asp polymorphism in IRS-2 with DM is correlated with occurrence of CAD. In multivariate logistic regression, employing non-diabetics with the Asp/Asp genotype as a reference group, the odds ratio for CAD was 1.561 [95% CI = 0.517-4.713, p = 0.430] for diabetics with the Asp/Asp genotype, 1.922 [95% CI = 1.086-3.400, p = 0.025] for non-diabetics with the Gly/Gly + Gly/Asp genotype, and 3.629 [95% CI = 1.820-7.236, p < 0.001] for diabetics with the Gly/Gly + Gly/Asp genotype. There was no association between Gly1057Asp polymorphism in IRS-2 and HOMA-IR index.
  
  
  CONCLUSIONS
  Gly allele at codon 1057 in IRS-2 is correlated with an increased susceptibility to CAD in the Taiwanese population. There is a synergistic effect toward CAD between the pathogenicity of DM and that of the Gly allele.
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. chansh@mail.ncku.edu.tw
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Chan
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Chen
authors.forename: Yi-Heng
authors.initials: YH
authors.lastname: Li
authors.forename: Liang-Miin
authors.initials: LM
authors.lastname: Tsai
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013624:Taiwan
chemical_list: D055504:Insulin Receptor Substrate Proteins; D005998:Glycine