251. Impact of Insulin Receptor Substrate-1 Genotypes on Platelet Reactivity and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
- Author
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Angiolillo, Dominick J., Bernardo, Esther, Zanoni, Martina, Vivas, David, Capranzano, Piera, Malerba, Giovanni, Capodanno, Davide, Prandini, Paola, Pasquali, Alessandra, Trabetti, Elisabetta, Sabaté, Manel, Jimenez-Quevedo, Pilar, Ferreiro, Jose L., Ueno, Masafumi, Bass, Theodore A., Pignatti, Pier Franco, Fernandez-Ortiz, Antonio, and Macaya, Carlos
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INSULIN receptors , *TYPE 2 diabetes , *CORONARY disease , *ASPIRIN , *CLOPIDOGREL , *GENETIC polymorphisms , *CYTOCHROME P-450 , *ADENOSINE diphosphate , *ANGIOPLASTY - Abstract
Objectives: The aim of this study was to assess the association between genetic variants of the insulin receptor substrate (IRS)-1 gene, platelet function, and long-term outcomes in patients with type 2 diabetes mellitus (DM) and stable coronary artery disease while on aspirin and clopidogrel therapy. Background: The effects of pharmacogenetic determinants on platelet function and cardiovascular outcomes in type DM patients are unknown. Methods: The association between IRS-1 genetic variants, platelet function, and the risk of major adverse cardiac events (MACE) at 2 years was assessed in 187 patients with type 2 DM and stable coronary artery disease on maintenance aspirin and clopidogrel therapy. Results: Seven tag single nucleotide polymorphisms were selected. Individuals with high platelet reactivity were more frequent among carriers of the C allele (GC and CC genotypes; approximately 20% of population) of the rs956115 marker (44.4% vs. 20.5%; odds ratio: 3.1, 95% confidence interval [CI]: 1.44 to 6.67; p = 0.006). These patients were at higher risk of MACE (28.0% vs. 10.9%; hazard ratio: 2.90, 95% CI: 1.38 to 6.11; p = 0.005). The C allele carriers of the rs956115 marker were more commonly associated with a hyperreactive platelet phenotype. This was confirmed in an external validation cohort of patients with type 2 DM but not in an external validation cohort of patients without DM. Carriers of the C allele of the rs956115 marker also had a significantly higher risk of MACE compared with noncarriers (30.6% vs. 11.4%; hazard ratio: 2.88, 95% CI: 1.35 to 6.14; p = 0.006). Conclusions: Type 2 DM patients who are carriers of the C allele of the rs956115 marker of the IRS-1 gene have a hyperreactive platelet phenotype and increased risk of MACE. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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