- 作者: Shih-Hung Chan, Jyh-Hong Chen, Yi-Heng Li and Liang-Miin Tsai
- 作者服務機構: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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.
Conclusion: 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. - 中文關鍵字: --
- 英文關鍵字: Insulin receptor substrate, Diabetes mellitus, Coronary artery disease, Single nucleotide polymorphism, Insulin resistance, Homeostasis model assessment