Abstract
BackgroundMyocardial 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.MethodsA 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.ResultsAfter 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).ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2261-14-170) contains supplementary material, which is available to authorized users.
Highlights
Myocardial infarction (MI) is a serious complication of Coronary Artery Disease (CAD)
There were no significant differences between the MI group and the control group in terms of mean body mass index (BMI) and distributions of ethnicity, hypertension and hyperlipidemia, while the mean age and frequencies of male gender, type 2 diabetes mellitus (T2DM)-positive, and smoking and drinking habits-positive were significantly higher in MI patients than in controls
The genotype distributions of the two SNPs between MI patients and controls and their association with MI risk are available in Table 2, while the univariate associations between each of the two SNPs and the clinical characteristics listed in Table 1 for cases and controls are included in the Additional file 1: Table S1 and S2
Summary
Myocardial infarction (MI) is a serious complication of Coronary Artery Disease (CAD). We 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. Genome-wide association studies (GWAS) have been a new approach since the completion of the Human Genome Project and the International HapMap Project, and have provided improved resolution in identifying genetic factors in relation to complex diseases. We chose to study SNP rs10757274 on chromosome 9p21 and SNP rs6903956 on chromosome 6p24, to identify the association between these two susceptible genes and the risk of MI, and to explore gene-environment interactions in a Chinese population
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