ASSOCIATION BETWEEN OSTEOPROTEGERIN GENE POLYMORPHISMS AND RISK OF CORONARY ARTERY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Jia P, Wu N, Jia D, Sun Y
*Corresponding Author: Professor Dalin Jia and/or Professor Yingxian Sun, Department of Cardiology, The First Affiliated Hospital of China Medical University, 155th North Nanjing Street, Heping District, Shenyang 110001, Liaoning Province, People’s Republic of China. Tel: +86-242-326-9477. Fax: +86-242-326-9477. Email: jdl2001@126.com and/or yxsun@mail.cmu.edu.cn
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DISCUSSION

Osteoprotegerin has been considered as a novel biomarker for predicting prevalence and severity of CAD [20]. Jono et al. [10] and Schoppet et al. [11] have demonstrated that serum OPG levels are associated with the presence and severity of CAD. Ren et al. [21] have further confirmed that increased plasma OPG levels are associated with the presence and severity of acute coronary syndrome. These studies suggest the potential prognostic utility of OPG as a biomarker in a clinical practice. In addition, some recent studies have found that several polymorphisms of the OPG gene, such as T950C and G1181C, are associated with the risk of CAD, but the results are still controversial [12-16]. Considering these inconsistent results, in this study, we performed meta-analysis to analyze the association between the G209A, T245G, T950C and G1181C polymorphisms of the OPG gene and the risk of CAD. G1181C is the most controversial in all polymorphisms of the OPG gene. Even in populations from the same country, the results are diverse [14,16]. The results of meta-analysis showed that the G1181C polymorphism was strongly associated with the risk of CAD with little heterogeneity across studies. In addition, the results also showed that the CC or CG genotypes may increase susceptibility to CAD, which agreed with previous findings [12]. The T950C polymorphism is located 233 bp upstream from the translation initiation site in the promoter region, and it could derive its functional significance by altering the promoter activity [13]. Previous research has demonstrated that T950C is the only polymorphism that is associated with serum OPG levels [12]. Our meta-analysis indicated that the T950C polymorphism was remarkably linked with the risk of CAD, which was consistent with previous results [12]. Moreover, we also reported that no association existed between G209A and T245G polymorphisms and the risk of CAD, which was in line with previous studies [14,15,19]. Similar to other meta-analyses, several limitations existed in our meta-analysis. First, the sample size is still relatively small and may not provide sufficient statistical power to estimate the correlation between the OPG gene polymorphisms and the susceptibility to CAD. More studies with larger sample size are still needed to accurately provide a more representative statistical analysis. Secondly, we did not evaluate the potential publication bias that may influence the result. Finally, although little heterogeneity exists, subgroup analysis should be performed to assess the association between the OPG gene polymorphisms and the susceptibility to CAD in different populations or countries. In conclusion, to the best of our knowledge, this meta-analysis is the first report to pool published studies to estimate the association between the OPG gene polymorphisms and the susceptibility to CAD. This study demonstrated that G1181C and T950C polymorphisms were strongly associated with the risk of CAD, but no association existed between G209A and T245G polymorphisms and the risk of CAD. Further large scale case-control studies with a rigorous design should be conducted to confirm the above conclusions in the future.



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