IRF6 Gene Polymorphisms Influence the Susceptibility of Nonsyndromic Cleft Lips With or Without Palate: A MOOSE-Compliant Meta-Analysis

Objective The present meta-analysis has been conducted with the objective of conducting a precise examination of the association between 6 IRF6 gene polymorphisms and the risk of nonsyndromic cleft lip with or without palate (CL ± P) among various ethnic groups. Methods The meta-analysis incorporated a total of 53 published case-control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed. A leave-1-out sensitivity analysis was conducted, in conjunction with an investigation into publication bias, under the dominant model. Subgroup analysis based on ethnicity was performed. Results The rs642961 was associated with an increased risk (AA + AG vs GG; OR: 1.31; 95% CI: 1.10-1.55; P < .02; I 2 = 70%), while rs2235371 significantly reduced risk (AA + AG vs GG; OR: 0.74; 95% CI: 0.60-0.92; P < .007; I 2 = 75%) of CL ± P. The remaining single-nucleotide polymorphisms (rs861019, rs2013162, rs2235373, and rs2235375) were not associated with the risk of CL ± P. Subgroup analysis based on ethnicity revealed distinct ethnicity-specific effects, with rs861019 associated with increased CL ± P risk in Caucasians, rs642961 increasing risk in Asians and mixed populations, and rs2235371 reducing risk only in Caucasians. Conclusion While IRF6 gene rs642961 and rs2235371 were found to be associated with an increased risk of CL ± P in all studies, there was suggestive evidence of ethnic-specific differences, particularly among Caucasian and Asian populations. Although this study lends further support to the notion of an association between CL ± P and the IRF6 gene polymorphisms, it is clear that further studies including diverse cohorts are needed to provide fully validated, ethnic- or population-specific insights.