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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?

SUBMITTER: Chan SH

PROVIDER: S-EPMC3541354 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Gly1057Asp polymorphism of insulin receptor substrate-2 is associated with coronary artery disease in the Taiwanese population.

Chan Shih-Hung SH Chen Jyh-Hong JH Li Yi-Heng YH Tsai Liang-Miin LM

Journal of biomedical science 20121205

<h4>Background</h4>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.<h4>Methods</h4>Patients receiving elective coronary angiography were enrolled. Significant stenosis is defined as a luminal diameter stenosis greater than 50%. Patients without significant stenosis ...[more]

PMID: 23216712

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Project description:Coronary artery disease (CAD) is a disease in which a waxy substance called plaque builds up inside the coronary arteries. Apelin is a novel endogenous peptide with inotropic and vasodilatory properties and is the ligand for the angiotensin receptor-like 1 (APJ) receptor. We aimed to determine genotype and allele frequencies of APJ receptor A445C gene polymorphism in Turkish patients with CAD and healthy controls by RFLP-PCR. This study was performed on 159 unrelated CAD patients and 62 healthy controls. We obtained AA, AC and CC genotype frequencies in CAD patients as 41.5%, 49.1% and 9.4%, respectively. In the control group, frequencies of genotypes were found as 35.5% for AA, 48.4% for AC and 16.1% for CC. We did not observe difference in APJ receptor A445C polymorphism between CAD patients and healthy controls (?(2) = 2.178; df = 2; P = 0.336). The A allele was encountered in 66% (210) of the CAD and 59.7% (74) of the controls. The C allele was seen in 34% (108) of the CAD and 40.3% (50) of the controls. Allele frequencies of interested genes were not significantly different between groups (?(2) = 1.57; df = 1; p = 0.225). The frequencies of APJ receptor A445C genotype were not significantly different between control and patients. None of the three APJ receptor A445C genotypes, AA, AC and CC displayed significant difference in CAD patients. We did not find any difference in the clinical parameters except for weight and diastolic blood pressure levels in the AA, AC and CC genotypes of patients. Individuals with CC genotypes had significantly higher weight, systolic and diastolic blood pressure levels and systolic blood pressure than other genotypes, P ? 0.05. In addition, HDL-C level was found decreased, but this reduction was not statistically significant. Contrarily, the low levels of weight, SBP, DBP and TC were statistically significant in the subjects with AA genotype in CAD. In conclusion, CC genotype carriers may have more risk than other genotypes in the development of hypertension in CAD, but not AAgenotype carriers. We suggest that this polymorphism may not be a marker of CAD, but it may cause useful in function of the apelin/APJ system and may be a genetic predisposing factor for diagnostic processes and can be helpfull in finding new treatment strategies. We think that it is required to further comprehensive studies in order to make clear this situation in CAD.

Dataset Information

Gly1057Asp polymorphism of insulin receptor substrate-2 is associated with coronary artery disease in the Taiwanese population.

Publications

Gly1057Asp polymorphism of insulin receptor substrate-2 is associated with coronary artery disease in the Taiwanese population.

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