Background: High platelet reactivity (HPR) has been associated with short- to mid-term atherothrombotic complications and cardiovascular events (CVE) even in patients taking combined aspirin and clopidogrel therapy. HPR is more frequent in patients with type 2 diabetes mellitus (T2DM) compared with non diabetic patients, even when treated with dual antiplatelet therapy. Whether HPR is associated with atherothrombotic complications and CVE in T2DM patients remains to be investigated. It has been widely observed that type 2 diabetes mellitus (T2DM) patients have an increased risk of developing cardiovascular events (CVE). Cardiovascular events include death secondary to cardiovascular cause, ST-segment elevation myocardial infarction (STEMI), non-ST –segment elevation acute coronary sindrome (NSTEMI), unstable angina and stroke. However, this risk is not homogeneous, which may be explained by genetic variances among these patients. The insulin receptor substrate-1 (IRS-1) gene has been recently investigated as a potential susceptibility factor, being involved in insulin resistance and impaired insulin secretion. The aim of this study was to evaluate if SNPs of the IRS-1 gene are associated with an increased probability of experiencing a CVE in T2DM patients. Methods: A total of 7 tagSNPs (rs1801278, rs11683087, rs1801123, rs1896832, rs956115, rs2251692, rs6725330) were determined in 180 T2DM patients with coronary artery disease on antiplatelet therapy with aspirin and clopidogrel. T2DM patients with CVE were collected during a 2-year follow-up period. Statistical analyses have been performed to assess a potential association between CVE and single SNPs genotypes or haplotypes by linkage disequilibrium blocks boundaries. Results: The 7 tagSNPs accounted for 93% of the haplotype distribution of the IRS-1 gene in Caucasians. CVE occurred in 20% of the study population. An association between carriers of the variant C allele of the rs956115 SNP and CVE at 2-years was observed (p=0.026). This association was also observed in the haplotype analyses including rs956115 and rs1896832 (p=0.0068). Conclusions: Genetic polymorphisms of the IRS-1 gene are associated with an enahnced risk of developing CVE in T2DM patients.

Association between genetic polymorphisms of the insulin receptor substrate-1 (IRS1) gene and cardiovascular events in type 2 diabetes mellitus patients

ZANONI, Martina;PRANDINI, PAOLA;MALERBA, Giovanni;TRABETTI, Elisabetta;PIGNATTI, Pierfranco
2008-01-01

Abstract

Background: High platelet reactivity (HPR) has been associated with short- to mid-term atherothrombotic complications and cardiovascular events (CVE) even in patients taking combined aspirin and clopidogrel therapy. HPR is more frequent in patients with type 2 diabetes mellitus (T2DM) compared with non diabetic patients, even when treated with dual antiplatelet therapy. Whether HPR is associated with atherothrombotic complications and CVE in T2DM patients remains to be investigated. It has been widely observed that type 2 diabetes mellitus (T2DM) patients have an increased risk of developing cardiovascular events (CVE). Cardiovascular events include death secondary to cardiovascular cause, ST-segment elevation myocardial infarction (STEMI), non-ST –segment elevation acute coronary sindrome (NSTEMI), unstable angina and stroke. However, this risk is not homogeneous, which may be explained by genetic variances among these patients. The insulin receptor substrate-1 (IRS-1) gene has been recently investigated as a potential susceptibility factor, being involved in insulin resistance and impaired insulin secretion. The aim of this study was to evaluate if SNPs of the IRS-1 gene are associated with an increased probability of experiencing a CVE in T2DM patients. Methods: A total of 7 tagSNPs (rs1801278, rs11683087, rs1801123, rs1896832, rs956115, rs2251692, rs6725330) were determined in 180 T2DM patients with coronary artery disease on antiplatelet therapy with aspirin and clopidogrel. T2DM patients with CVE were collected during a 2-year follow-up period. Statistical analyses have been performed to assess a potential association between CVE and single SNPs genotypes or haplotypes by linkage disequilibrium blocks boundaries. Results: The 7 tagSNPs accounted for 93% of the haplotype distribution of the IRS-1 gene in Caucasians. CVE occurred in 20% of the study population. An association between carriers of the variant C allele of the rs956115 SNP and CVE at 2-years was observed (p=0.026). This association was also observed in the haplotype analyses including rs956115 and rs1896832 (p=0.0068). Conclusions: Genetic polymorphisms of the IRS-1 gene are associated with an enahnced risk of developing CVE in T2DM patients.
2008
IRS-1 gene; genetic association; cardiovascular events; type 2 diabetes mellitus
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/340753
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