20q12 rs13041247 多态性与非综合征型唇裂伴或不伴腭裂风险的关联：一项荟萃分析。

BACKGROUND: Previous genome-wide association studies have identified a link between the rs13041247 single nucleotide polymorphisms (SNPs) in the chromosome 20q12 locus and the development of the congenital malformation known as nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present meta-analysis was therefore designed to formally assess the relationship between rs13041247 and NSCL/P. METHODS: We searched Embase, Web of Science, PubMed, the China National Knowledge Internet (CNKI), and the China Wanfang database in order to identify relevant published through 25 June 2019. This allowed us to identify 13 studies incorporating 4914 patients and 5981 controls for whom rs13041247 genotyping had been conducted, with STATA 12.0 then being used to conduct a meta-analysis of these pooled results. The I statistic was used to compare heterogeneity among studies. RESULTS: In total this analysis incorporated 13 case-control studies. No association between the rs13041247 polymorphism and NSCL/P risk was detected in individuals of Asian ethnicity (C vs T: OR = 0.847, 95% CI = 0.702-1.021; CC vs TT: OR = 0.725, 95% CI = 0.494-1.063; CC vs CT: OR = 0.837, 95% CI = 0.657-1.067; CT + TT vs CC: OR = 1.265, 95% CI = 0.951-1.684; CC + CT vs TT: OR = 0.805, 95% CI = 0.630-1.029) or Caucasian ethnicity (C vs T: OR = 0.936, 95% CI = 0.786-1.114; CC vs TT: OR = 0.988, 95% CI = 0.674-1.446; CC vs CT: OR = 1.197, 95% CI = 0.816-1.757; CT + TT vs CC: OR = 0.918, 95% CI = 0.639-1.318; CC + CT vs TT: OR = 0.855, 95% CI = 0.677-1.081). However, an overall analysis of all participants in these studies revealed the rs13041247 C allele, the CT genotype, and the CC + CT model to be linked to a reduced NSCL/P risk (C vs T: OR = 0.897, 95% CI: 0.723-1.114, P = 0.048; CT vs TT: OR = 0.839, 95% CI: 0.734-0.959, P = 0.01; CC + CT vs TT: OR = 0.824, 95% CI: 0.701-0.968, P = 0.019). CONCLUSION: These results suggest that the rs13041247 SNP located at the 20q12 chromosomal locus is associated with NSCL/P risk in an overall pooled study population, although this association was not significant in East Asian or Caucasian populations.

背景：先前的全基因组关联研究已经确定了 20q12 染色体上的 rs13041247 单核苷酸多态性（SNP）与先天性畸形非综合征性唇裂伴或不伴腭裂（NSCL/P）的发展之间存在关联。因此，本荟萃分析旨在正式评估 rs13041247 与 NSCL/P 之间的关系。

方法：我们检索了 Embase、Web of Science、PubMed、中国国家知识基础设施（CNKI）和中国万方数据库，以确定截至 2019 年 6 月 25 日发布的相关研究。这使我们能够识别出 13 项纳入了 4914 名患者和 5981 名对照者的研究，这些研究对 rs13041247 进行了基因分型，并使用 STATA 12.0 对这些汇总结果进行了荟萃分析。I 统计用于比较研究之间的异质性。

结果：这项分析共纳入了 13 项病例对照研究。在亚洲人群中，未发现 rs13041247 多态性与 NSCL/P 风险之间存在关联（C 对 T：OR=0.847，95%CI=0.702-1.021；CC 对 TT：OR=0.725，95%CI=0.494-1.063；CC 对 CT：OR=0.837，95%CI=0.657-1.067；CT+TT 对 CC：OR=1.265，95%CI=0.951-1.684；CC+CT 对 TT：OR=0.805，95%CI=0.630-1.029）或高加索人群（C 对 T：OR=0.936，95%CI=0.786-1.114；CC 对 TT：OR=0.988，95%CI=0.674-1.446；CC 对 CT：OR=1.197，95%CI=0.816-1.757；CT+TT 对 CC：OR=0.918，95%CI=0.639-1.318；CC+CT 对 TT：OR=0.855，95%CI=0.677-1.081）。然而，对这些研究所有参与者的总体分析显示，rs13041247 C 等位基因、CT 基因型和 CC+CT 模型与 NSCL/P 风险降低相关（C 对 T：OR=0.897，95%CI：0.723-1.114，P=0.048；CT 对 TT：OR=0.839，95%CI：0.734-0.959，P=0.01；CC+CT 对 TT：OR=0.824，95%CI：0.701-0.968，P=0.019）。

结论：这些结果表明，位于 20q12 染色体位置的 rs13041247 SNP 与总体研究人群的 NSCL/P 风险相关，尽管在东亚或高加索人群中这种关联并不显著。