Angiolillo, Dominick JBernardo, EstherVivas Balcones, Luis DavidSabaté, ManelJimenez Quevedo, PilarFernández Ortiz, Antonio IgnacioMacaya Miguel, Carlos2024-02-072024-02-072011-06-28Angiolillo 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;58:30-90735-109710.1016/j.jacc.2011.02.040https://hdl.handle.net/20.500.14352/99783Estudio 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.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.engjournal articlehttps://www.sciencedirect.com/science/article/pii/S0735109711013428?via%3Dihub21700086https://pubmed.ncbi.nlm.nih.gov/21700086/restricted access616.1/.9Antiplatelet therapyDiabetes mellitusGenePlatelet functionCiencias Biomédicas32 Ciencias Médicas