BMP4 rs17563 polymorphism and nonsyndromic cleft lip with or without cleft palate: A meta-analysis

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.