- 作者：Dominick J. Angiolillo MD ; PhD ; dominick.angiolillo@jax.ufl.edu"" rel=""nofollow ; Esther Bernardo BSc† ; ; Martina Zanoni PhD‡ ; ; David Vivas MD ; PhD† ; ; Piera Capranzano MD ; Giovanni Malerba PhD‡ ; ; Davide Capodanno MD ; Paola Prandini PhD‡ ; ; Alessandra Pasquali PhD‡ ; ; Elisabetta Trabetti PhD‡ ; ; Manel Sabaté ; MD ; PhD† ; ; Pilar Jimenez-Quevedo MD ; PhD† ; ; Jose L. Ferreiro MD ; Masafumi Ueno MD ; Theodore A. Bass MD ; Pier Franco Pignatti MD‡ ; ; Antonio Fernandez-Ortiz MD ; PhD† ; ; Carlos Macaya MD ; PhD† ;
- 关键词：antiplatelet therapy ; diabetes mellitus ; gene ; platelet function
- 刊名：Journal of the American College of Cardiology
- 出版年：2011
- 出版时间：28 June 2011
- 年：2011
- 卷：58
- 期：1
- 页码：30-39
- 全文大小：737 K
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.