Abstract
Background: The previous published data on the association between interferon regulatory factor 6 (IRF6) polymorphisms and non-syndromic Cleft Lip/Palate (NSCL ± P) risk remained inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations.
 Methods: A comprehensive search in PubMed, EMBASE, Web of Science, and CNKI for all eligible studies up July 2021.
 Results: A total of 23 studies with 6,161 cases and 8,919 controls were selected for this meta-analysis. Overall pooled analysis suggest a significant association between IRF6 rs2235371 polymorphism and CL±P risk under all the five genetic models, i.e., allele (A vs. G: OR=0.754, 95% CI 0.628-0.905, P=0.002), homozygote (AA vs. GG: OR=0.621 95% 0.405-0.953, P=0.029), heterozygote (AC vs. GG: OR=0.619, 95% CI 0.485-0.791, P≤0.001), dominant (AA+AG vs. GG: OR=0.550, 95% CI 0.381-0.794, P=0.001) and recessive model (AA vs. AG+GG: OR=0.583, 95% CI 0.423-0.804, P=0.001). Subgroup analysis by ethnicity showed that rs2235371 was associated with NSCL±P risk in Asians.
 Conclusion: This meta-analysis provides strong evidences that IRF6 rs2235371 might be associated with risk of NSCL ± P.
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