Li Yue-Hua, Yang Jiaomei, Zhang Ju-Lei, Liu Jia-Qi, Zheng Zhao, Hu Da-Hai
Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University Department of Epidemiology and Health Statistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Medicine (Baltimore). 2017 Aug;96(31):e7676. doi: 10.1097/MD.0000000000007676.
Previous studies have investigated the relationship between human bone morphogenetic protein 4 gene (BMP4) rs17563 polymorphism and nonsyndromic cleft lip with or without cleft palate (NSCL/P). However, the results remained inconsistent. Therefore, we conducted a meta-analysis to assess the effect of BMP4 rs17563 polymorphism on NSCL/P.
Electronic searches in 5 databases were conducted to select all eligible studies up to March 2017. Odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated to estimate the association. Sensitivity analysis was performed to evaluate the results stability by excluding each study in turn. Publication bias was assessed by Begg funnel plots and Egger test.
A total of 11 case-control studies were included in the meta-analysis. The pooled frequency of the minor allele C for BMP4 rs17563 was lower in Asians (pooled frequency = 0.33, 95% CI: 0.29-0.37) than in Brazilian population (pooled frequency = 0.47, 95% CI: 0.40-0.54). The overall results showed no significant association of BMP4 rs17563 polymorphism with NSCL/P risk. However, the results turned out to be different when stratified by ethnicity. BMP4 rs17563 polymorphism was associated with a higher risk of NSCL/P among Asian ethnicity (C vs T: OR = 1.33, 95% CI: 1.02-1.73; CC vs TT: OR = 2.10, 95% CI: 1.28-3.43; CC vs TT + TC: OR = 2.16, 95% CI: 1.34-3.47) and among Caucasian population (TC vs TT: OR = 3.36, 95% CI: 2.03-5.54; TC + CC vs TT: OR = 3.71, 95% CI: 2.43-5.69). Among Brazilian population, BMP4 rs17563 polymorphism exerted a significantly protective effect on NSCL/P (C vs T: OR = 0.70, 95% CI: 0.58-0.84; CC vs TT: OR = 0.54, 95% CI: 0.33-0.88; TC vs TT: OR = 0.55, 95% CI: 0.44-0.69; TC + CC vs TT: OR = 0.56, 95% CI: 0.45-0.69).
The results suggest that the C allele of BMP4 rs17563 may be a risk factor for NSCL/P among Asians and Caucasians, and may be a protective factor for NSCL/P in Brazilian population. Future large-sample studies with appropriate designs among specific populations are warranted to evaluate the association.
既往研究探讨了人类骨形态发生蛋白4基因（BMP4）rs17563多态性与非综合征性唇裂伴或不伴腭裂（NSCL/P）之间的关系。然而，结果仍不一致。因此，我们进行了一项荟萃分析，以评估BMP4 rs17563多态性对NSCL/P的影响。
对5个数据库进行电子检索，以选择截至2017年3月的所有符合条件的研究。计算比值比（OR）及相应的95%置信区间（CI）以评估关联。通过逐一排除每项研究进行敏感性分析，以评估结果的稳定性。采用Begg漏斗图和Egger检验评估发表偏倚。
荟萃分析共纳入11项病例对照研究。BMP4 rs17563次要等位基因C在亚洲人中的合并频率（合并频率=0.33，95%CI：0.29-0.37）低于巴西人群（合并频率=0.47，95%CI：0.40-0.54）。总体结果显示，BMP4 rs17563多态性与NSCL/P风险无显著关联。然而，按种族分层时结果有所不同。BMP4 rs17563多态性在亚洲种族中与NSCL/P风险较高相关（C vs T：OR=1.33，95%CI：1.02-1.73；CC vs TT：OR=2.10，95%CI：1.28-3.43；CC vs TT+TC：OR=2.16，95%CI：1.34-3.47），在白种人群中也如此（TC vs TT：OR=3.36，95%CI：2.03-5.54；TC+CC vs TT：OR=3.71，95%CI：2.43-5.69）。在巴西人群中，BMP4 rs17563多态性对NSCL/P具有显著的保护作用（C vs T：OR=0.70，95%CI：0.58-0.84；CC vs TT：OR=0.54，95%CI：0.33-0.88；TC vs TT：OR=0.55，95%CI：0.44-0.69；TC+CC vs TT：OR=0.56，95%CI：0.45-0.69）。
结果表明，BMP4 rs17563的C等位基因可能是亚洲人和白种人中NSCL/P的危险因素，而在巴西人群中可能是NSCL/P的保护因素。有必要在特定人群中开展未来的大样本、设计合理的研究以评估这种关联。
