NKX2-5 基因的两个遗传变异与中国人群先天性心脏病风险的关联：荟萃分析。

Associations between two genetic variants in NKX2-5 and risk of congenital heart disease in Chinese population: a meta-analysis.

机构信息

Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health (Incubation), Ministry of Environmental Protection Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

PLoS One. 2013 Aug 2;8(8):e70979. doi: 10.1371/journal.pone.0070979. Print 2013.

DOI:10.1371/journal.pone.0070979

PMID:23936479

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3732287/

Abstract

BACKGROUND

NKX2-5 is a transcriptional factor, which plays an important role in heart formation and development. Two genetic variants in the coding region of NKX2-5, 63A>G (rs2277923) and 606G>C (rs3729753), have been investigated in the risk of congenital heart disease (CHD), although with inconsistent results. Thus, a meta-analysis was performed to clarify the associations between the two variants and CHD risk in the Chinese population.

METHODS AND RESULTS

Relevant studies were identified by searching PubMed, ISI Web of Science and CNKI databases and by reviewing the reference lists of retrieved articles. Then, the data from eligible studies were combined in an allelic model. A total of 7 and 4 studies were ultimately included for 63A>G and 606G>C, respectively. The results of overall meta-analyses showed that significant association was detected for 63A>G (OR = 1.26, 95% CI = 1.02-1.56, P(heterogeneity )= 0.009, I (2) = 65.1%), but not for 606G>C (OR = 1.22, 95% CI = 0.75-1.96, P(heterogeneity )= 0.412, I (2) = 0.0%). Regarding 63A>G variant, positive results were also obtained in the subgroups of atrial septal defect and large-sample-size study. Besides, the sensitivity analysis indicated that significant association was still detected after deletion of the individual studies with positive result and striking heterogeneity.

CONCLUSION

Our results revealed that the 63A>G variant in NKX2-5, but not the 606G>C, may contribute to CHD risk for Chinese.

摘要

背景

NKX2-5 是一种转录因子，在心脏形成和发育中发挥重要作用。已经研究了 NKX2-5 编码区中的两个遗传变异，63A>G（rs2277923）和 606G>C（rs3729753），它们与先天性心脏病（CHD）的风险有关，尽管结果不一致。因此，进行了荟萃分析以阐明这两种变异与中国人群 CHD 风险之间的关系。

方法和结果

通过搜索 PubMed、ISI Web of Science 和 CNKI 数据库并查阅检索文章的参考文献列表，确定了相关研究。然后，将合格研究的数据合并为等位基因模型。最终分别纳入了 7 项和 4 项研究用于 63A>G 和 606G>C。总体荟萃分析的结果表明，63A>G 存在显著相关性（OR=1.26，95%CI=1.02-1.56，P（异质性）=0.009，I（2）=65.1%），但 606G>C 无显著相关性（OR=1.22，95%CI=0.75-1.96，P（异质性）=0.412，I（2）=0.0%）。对于 63A>G 变异，在房间隔缺损亚组和大样本量研究中也得到了阳性结果。此外，敏感性分析表明，在删除具有阳性结果和显著异质性的个别研究后，仍然存在显著相关性。