Impact of Insulin Receptor Substrate‐1 rs956115 and CYP2C19 rs4244285 Genotypes on Clinical Outcome of Patients Undergoing Percutaneous Coronary Intervention
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Overview
abstract
Background
Insulin receptor substrate‐1 (
IRS‐1
) rs956115 is associated with vascular risk in patients with coronary artery disease and concomitant diabetes.
CYP2C19*2
(rs4244285) modulates clopidogrel response and predicts the outcome of coronary artery disease. This study was designed to explore the association between
IRS‐1
,
CYP2C19*2
genotypes, platelet reactivity, and 1‐year outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.
Methods and Results
Genotyping was performed using an improved multiplex ligation detection reaction technique. Platelet aggregation was assessed by light transmission aggregometry. Major adverse cardiovascular events were defined as a composite of cardiovascular death, myocardial infarction, and ischemic stroke. A total of 2213 consecutive patients were screened and 1614 were recruited. At 1 month, patients with
IRS‐1
CG genotype had significantly lower levels of ADP‐induced platelet aggregation compared with patients with CC homozygotes. Patients with
IRS‐1
CG or GG genotype had a 2.09‐fold higher risk of major adverse cardiovascular events compared with those with CC homozygotes (95% CI, 1.04–4.19;
P
=0.0376). By comparison, patients with
CYP2C19*2
GA or AA genotype had higher ADP‐induced platelet aggregation compared with patients with GG homozygotes. Although there was no significant difference in risk of major adverse cardiovascular events between patients with GA/AA and GG genotypes, patients with GA genotype had a 2.19‐fold higher risk than those with GG homozygotes (95% CI, 1.13–4.24;
P
=0.0200). No interaction between
IRS‐1
and
CYP2C19*2
genotypes was observed.
Conclusions
In patients following percutaneous coronary intervention,
IRS‐1
GG/CG and
CYP2C19*2
GA genotypes were associated with 2.09‐ and 2.19‐fold increased cardiovascular risk, respectively, at 1‐year follow‐up. The association between
IRS‐1
genotypes and major adverse cardiovascular events appeared to be independent of known clinical predictors.
Registration
URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01968499.
