Association of Thrombomodulin Gene Polymorphisms with Susceptibility to Atherosclerotic Diseases: A Meta-Analysis

Previous studies have proved that the dysfunction of thrombomodulin (TM) plays an important role in the pathogenesis of atherosclerotic diseases. In order to reveal their inherent relationship, we conducted a meta-analysis to uncover the association between two polymorphisms -33G/A and Ala455Val (c.1418C>T) in the TM gene and atherosclerotic diseases. We carried out a systematic search in PubMed, Science Direct, BIOSIS Previews, SpringerLink, the Cochrane library, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Database, the Wei Pu database, and the Wanfang Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed to show the association. We included 22 eligible studies which involved 5472 patients and 7786 controls. There were statistically significant associations between -33G/A polymorphisms in TM and the MI group under the Allele and Recessive models in Asians (G vs. A: OR = 0.67, 95%CI = 0.56-0.78, P < 0.00001; GG vs. GA+AA: OR = 0.66, 95%CI = 0.56-0.78, P < 0.00001). However, these findings of the overall and subgroups showed that Ala455Val polymorphisms did not have any relationship with atherosclerotic diseases. After Bonferroni correction, the above associations remained statistically significant. This meta-analysis provides robust evidence of association between the -33G/A polymorphism in the TM gene and the risk of myocardial infarction in Asians. The A allele may increase the incidence of MI in Asians. However, the Ala455Val variant was not associated with atherosclerotic risk. Further studies with adequate sample size are needed to verify our findings.