Chromosome 9p21 single nucleotide polymorphisms are not associated with recurrent myocardial infarction in patients with established coronary artery disease.

Center of Excellence, Health Services Research and Development, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA.
Circulation Journal (Impact Factor: 3.58). 02/2012; 76(4):950-6. DOI: 10.1253/circj.CJ-11-1166
Source: PubMed

ABSTRACT Chromosome 9p21 single nucleotide polymorphisms (SNPs) have been shown to be associated with coronary heart disease in multiple studies. The aim of the present study was to identify whether these SNPs are associated with recurrent myocardial infarction (MI), revascularization, or death in acute coronary syndrome (ACS) patients or in those undergoing coronary artery bypass grafting (CABG).
TexGen registry participants with ACS (n=2,067) or CABG (n=1,176) were evaluated, to assess whether 9p21 SNPs (rs1333049, rs2383206, rs10757278, rs10757274) were associated with recurrent MI (primary outcome), recurrent revascularization, or death (secondary outcomes) at approximately 3.2 years of follow-up. Carriers of risk allele (C) for rs1333049 presented at an earlier age (62 vs. 63.5 years in non-carriers, P=0.0004) with more extensive disease (number of vessels with significant stenosis: 1.9 vs. 1.7 in non-carriers, P=0.001) in the ACS group. In adjusted models, the C allele was not associated with recurrent MI (hazard ratio [HR], 1.01; 95% confidence interval [CI]: 0.74-1.38), recurrent revascularization (HR, 0.98; 95%CI: 0.78-1.23), or death (HR, 0.91; 95%CI: 0.69-1.18) in the ACS or CABG groups (recurrent MI: HR, 0.64; 95%CI: 0.40-1.05; recurrent revascularization: HR, 0.98; 95%CI: 0.61-1.55; death: HR, 0.89; 95%CI: 0.61-1.30). Results were similar for the other 3 SNPs.
9p21 SNPs were not associated with recurrent MI, revascularization, or mortality after ACS or CABG. Individuals with the rs1333049 C allele, however, may present with earlier and more extensive disease.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Myocardial infarction (MI) is a serious complication of Coronary Artery Disease (CAD). Previous studies have identified genetic variants on chromosome 9p21 and 6p24 that are associated with CAD, but further studies need to be conducted to investigate whether these genetic variants are associated with the pathogenesis of MI. We therefore performed this study to assess the association between the risk of MI and SNP rs10757274 on chromosome 9p21 and SNP rs6903956 on chromosome 6p24, and to explore the gene-environment interactions in a Chinese population. A hospital-based case-control study, consisting of 502 MI patients and 308 controls, was conducted in a Chinese population. Demographic, behavioral information and clinical characteristics were collected, and genotyping of the two SNPs was performed using single base primer extension genotyping technology. The unconditional logistic regression (ULR) method was adopted to assess the association of the two SNPs with MI risk. Both generalized multifactor dimensionality reduction (GMDR) and ULR methods were applied to explore the effect of gene-environment interactions on the risk of MI. After adjusting for covariates, it was observed that SNP rs10757274 on chromosome 9p21 was significantly associated with MI. Compared with subjects carrying the AA genotype, subjects carrying the GA or GG genotypes had a higher MI risk (ORa = 1.52, 95%CI:1.06-2.19, pa = 0.0227; ORa = 2.40, 95%CI:1.51-3.81, pa = 0.0002, respectively). Furthermore, a two-factor gene-environment interaction model of CDKN2A/B (rs10757274) and type 2 diabetes mellitus (T2DM) was identified to be the best model by GMDR (p = 0.0107), with a maximum prediction accuracy of 59.18%, and a maximum Cross-validation Consistency of 10/10. By using the ULR method, additive interaction analysis found that the combined effect resulted in T2DM-positive subjects with genotype GG/GA having an MI risk 4.38 times that of T2DM-negative subjects with genotype AA (ORadd = 4.38, 95%CI:2.56-7.47, padd < 0.0001). These results show that gene polymorphism of CDKN2A/B (rs10757274) is associated with MI risk in a Chinese population. Furthermore, T2DM is likely to have an interaction with CDKN2A/B (rs10757274) that contributes to the risk of MI.
    BMC Cardiovascular Disorders 11/2014; 14(1):170. · 1.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Studies suggest that the 9p21-3 locus may influence susceptibility to myocardial infarction. We performed a systematic review and meta-analysis to assess whether this locus is associated with severity of coronary atherosclerosis and adverse clinical outcomes in those with known coronary disease.
    BMC Medical Genetics 06/2014; 15(1):66. · 2.54 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Chromosome 9p21 single nucleotide polymorphism (SNP) is a susceptibility variant for acute myocardial infarction (AMI) in the primary prevention setting. However, it is controversial whether this SNP is also associated with recurrent myocardial infarction (ReMI) in the secondary prevention setting. The purpose of this study is to evaluate the impact of chromosome 9p21 SNP on ReMI in patients receiving secondary prevention programmes after AMI. Design: A prospective observational study. Setting: Osaka Acute Coronary Insufficiency Study (OACIS) in Japan. Participants: 2022 patients from the OACIS database. Interventions: Genotyping of the 9p21 rs1333049 variant. Primary outcome measures: ReMI event after survival discharge for 1 year. Results: A total of 43 ReMI occurred during the 1 year follow-up period. Although the rs1333049 C allele had an increased susceptibility to their first AMI in an additive model when compared with 1373 healthy controls (OR 1.20, 95% CI 1.09 to 1.33, p=2.3*10−4), patients with the CC genotype had a lower incidence of ReMI at 1 year after discharge of AMI (log-rank p=0.005). The adjusted HR of the CC genotype as compared with the CG/GG genotypes was 0.20 (0.06 to 0.65, p=0.007). Subgroup analysis demonstrated that the association between the rs1333049 CC genotype and a lower incidence of 1 year ReMI was common to all subgroups. Conclusions: Homozygous carriers of the rs1333049 C allele on chromosome 9p21 showed a reduced risk of 1 year ReMI in the contemporary percutaneous coronary intervention era, although the C allele had conferred susceptibility to their first AMI.
    BMJ Open 08/2014; 4:e005438. · 2.06 Impact Factor