Abstract
Large-scale genome-wide association studies (GWAS) have revealed that rs10757278 polymorphism (or its proxy rs1333049) on chromosome 9p21 is associated with myocardial infarction (MI) susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported weak or no significant association. Here, we reevaluated this association using large-scale samples by searching PubMed and Google Scholar databases. Our results showed significant association between rs10757278 polymorphism and MI with p = 6.09 × 10−22, odds ratio (OR) = 1.29, 95% confidence interval (CI) 1.22–1.36 in pooled population. We further performed a subgroup analysis, and found significant association between rs10757278 polymorphism and MI in Asian and Caucasian populations. We identified that the association between rs10757278 polymorphism and MI did not vary substantially by excluding any one study. However, the heterogeneity among the selected studies varies substantially by excluding the study from the Pakistan population. We found even more significant association between rs10757278 polymorphism and MI in pooled population, p = 3.55 × 10−53, after excluding the study from the Pakistan population. In summary, previous studies reported weak or no significant association between rs10757278 polymorphism and MI. Interestingly, our analysis suggests that rs10757278 polymorphism is significantly associated with MI susceptibility by analyzing large-scale samples.
Highlights
Myocardial infarction (MI) is a complex human disease with a strong genetic component [1]
genome-wide association studies (GWAS) and candidate gene studies investigated the association between rs10757278 polymorphism and MI in other populations
Our results showed significant association between rs10757278 polymorphism and MI with p = 6.09 × 10−22, odds ratio (OR) = 1.29, 95% confidence interval (CI) 1.22–1.36 (Figure 2)
Summary
Myocardial infarction (MI) is a complex human disease with a strong genetic component [1]. Genome-wide association studies (GWAS) are considered to be new and powerful approaches to detect the genetic variants of human complex diseases. Helgadottir et al investigated a total of 4587 MI cases and 12,767 controls [3]. They identified variant rs10757278 on chromosome 9p21, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with MI with high significance (p = 1.00 × 10−20, odds ratio (OR) = 1.28, 95% confidence interval (CI) 1.22–1.35) [3]. Considering the important role of rs10757278 polymorphism in MI risk and inconsistent results reported by previous studies, we reevaluated this association using a meta-analysis method by searching the PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar databases (http://scholar.google.com/)
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