Abstract 4011: Influence Of Rs1333040, A Newly Discovered 9p21.3 Genetic Variant, On Clinical Outcomes In Early-onset Myocardial Infarction
Background and objective The association between few common genetic variants on chromosomal region 9p21.3 and myocardial infarction has been recently identified by genome-wide association studies. In the present study we sought to replicate the association of five 9p21.3 single nucleotide polymorphisms (SNPs) with early-onset myocardial infarction and we investigated the influence of the best tag SNP on the reoccurrence of cardiovascular events during long-term follow-up.
Methods The Italian genetic study of early-onset myocardial infarction is a nationwide prospective study involving 1842 patients hospitalised for a first myocardial infarction before the age of 45 years followed up for cardiovascular events. Genotyping was performed using a Sequenome MassARRAY platform.
Results All the five 9p21.3 genetic variants (rs10116277, rs1333040, rs2383206, rs10757278, and rs133049) were significantly associated with early-onset myocardial infarction (p<0.001 for all), being rs133040 the variant with the strongest signal of association (p= 0.0000006). Rs133040 significantly departed from a multiplicative model of the effect in a recessive direction (p=0.03) with a homozygous OR of 1.56 (95% confidence interval 1.29 to 1.89, p=0.000004) after adjusting for traditional risk factors. The homozygous rs1333040 genotype had a significant influence on the evolution of coronary artery disease after the first myocardial infarction, with a 1.9-fold increase (95% Bayesian credible interval 1.37 to 2.8) in the rate of surgical revascularizations and a 1.29-fold increase (95% credible interval 1.02 to 1.71) in that for percutaneous revascularisations. These estimates are adjusted for the joint effect of traditional risk factors and coronary artery severity at first myocardial infarction. There was no evidence of a marginal association of the same genotype with the risk of cardiovascular death or the reoccurrence of myocardial infarction.
Conclusions The 9p21.3 genetic variant rs133040 predicts the need for coronary artery by-pass surgery and for percutaneous revascularisation during long-term follow-up. Therefore, the rs1333040 9p21.3 genetic variant influences a clinical outcome that is related to the progression of coronary atherosclerosis.