RT Journal Article
T1 Impact of insulin receptor substrate-1 genotypes on platelet reactivity and cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease
A1 Angiolillo, Dominick J
A1 Bernardo, Esther
A1 Vivas Balcones, Luis David
A1 Sabaté, Manel
A1 Jimenez Quevedo, Pilar
A1 Fernández Ortiz, Antonio Ignacio
A1 Macaya Miguel, Carlos
AB 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.
PB Elsevier
SN 0735-1097
YR 2011
FD 2011-06-28
LK https://hdl.handle.net/20.500.14352/99783
UL https://hdl.handle.net/20.500.14352/99783
LA eng
NO Angiolillo DJ, Bernardo E, Zanoni M, Vivas D, Capranzano P, Malerba G, et al. Impact of insulin receptor substrate-1 genotypes on platelet reactivity and cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol. 2011;58:30-9
NO Estudio observacional prospectivo donde se evaluaron 187 pacientes con enfermedad coronaria estable y diabetes mellitus y su respuesta a la inhibición plaquetaria con clopidogrel en función de las variaciones genéticas del receptor de substrato insulínico-1 de la plaqueta. El estudió concluyó que los portadores del alelo C en el marcador rs956115 del gen que codifica el receptor IRS-1 presenta mayor reactividad plaquetaria y un mayor riesgo de presentar eventos cardiovasculares.
DS Docta Complutense
RD 18 abr 2025