Association between IRF6 and 8q24 polymorphisms and nonsyndromic cleft lip with or without cleft palate: Systematic review and meta‐analysis

BACKGROUND: We conducted a systematic review and meta‐analysis of interferon regulatory factor 6 and 8q24 polymorphisms with nonsyndromic cleft lip with/without cleft palate (NSCL/P). METHODS: Data extraction was independently performed by two reviewers. Genotypic effects of four polymorphisms from 31 studies were pooled separately by ethnicity using a mixed‐effect logit model with accounting for heterogeneity. RESULTS: For rs2235371, AA and GA carried, respectively, 51% (95% confidence interval [CI], 37%–61%) and 42% (95% CI, 32%–50%) lower risks of NSCL/P than GG genotypes in Asians, but these genotypes were not significant in Caucasians. For rs2013162, only AA was significant, that is, carried 0.65 (95% CI, 0.52–0.82) times lower odds than CC in Caucasians but not for Asians. For rs642961, AA and GA genotypes, respectively, carried 2.47 (95% CI, 1.41–4.35) and 1.40 (95% CI, 1.12–1.75) times higher odds in Asian, and 2.03 (95% CI, 1.52–2.71) and 1.58 (95% CI, 1.37–1.82) times higher odds in Caucasians compare with GG genotypes. For rs987525, AA and CA genotypes carried 2.27 (95% CI, 1.43–3.60) and 1.34 (95% CI, 1.02–1.77) times higher odds in Asian, and 5.25 (95% CI, 3.98–6.91) and 2.13 (95% CI–1.82, 2.49) times higher odds in Caucasians, and 1.42 (95% CI, 1.10–1.82) and 1.28 (95% CI, 1.09–1.50) times higher odds in mixed ethnicities compared with CC genotypes. These variant effects remained significant based on applying Bonferroni corrected‐thresholds, except in the mixed ethnicity. CONCLUSION: We show robust variant effects in NSCL/P. Considering them with other genes and risk factors might be useful to improve prediction of NSCL/P occurrence. Birth Defects Research (Part A) 106:773–788, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc.