A comprehensive consolidation of data on the relationship between IRF6 polymorphisms and non-syndromic cleft lip/palate susceptibility: From 79 case-control studies

Background: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent craniofacial birth defect on a global scale. A number of candidate genes have been identified as having an impact on NSCL/P. However, the association between interferon regulatory factor 6 (IRF6) polymorphisms and NSCL/P has yielded inconsistent results, prompting the need for a meta-analysis to obtain more accurate estimates.

Methods: We conducted a thorough screening of all relevant articles published up until November 15, 2023, in online bibliographic databases. The statistical analysis of the collected data was performed using the Comprehensive Meta-Analysis (Version 4.0) software.

Results: A total of 79 case-control studies, comprising 14,003 cases and 19,905 controls, were included in our analysis. The combined data indicated that the IRF6 rs642961 and rs2235371 polymorphisms were associated with an increased risk of NSCL/P in the overall population. However, no significant association was found between the rs2013162 and rs2235375 polymorphisms and the risk of NSCL/P in the overall population. Furthermore, subgroup analyses revealed significant correlations between the IRF6 rs642961, rs2235371, and rs2235375 polymorphisms and the risk of NSCL/P based on ethnic background and country of origin. Nevertheless, the rs2013162 polymorphism plays a protective role in Caucasians and mixed populations.

Conclusions: Our collective data indicates a significant association between the rs642961 and rs2235371 polymorphisms and the risk of NSCL/P in the overall population. The rs2235375 polymorphism could influence the susceptibility to NSCL/P based on ethnic background. Meanwhile, the rs2013162 polymorphism provides protective effects in Caucasian, mixed populations, and the Brazilian population.