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

• Published in: Birth defects research. A Clinical and molecular teratology Vol. 106; no. 9; pp. 773 - 788
• Main Authors: Wattanawong, Kachin, Rattanasiri, Sasivimol, McEvoy, Mark, Attia, John, Thakkinstian, Ammarin
• Format: Journal Article
• Language: English
• Published: United States 01.09.2016
• Subjects: 8q24; Asian Continental Ancestry Group; Chromosomes, Human, Pair 8 - genetics; Cleft Lip - ethnology; Cleft Lip - genetics; Cleft Palate - etiology; Cleft Palate - genetics; European Continental Ancestry Group; Female; Genotype; Humans; Interferon Regulatory Factors - genetics; IRF6; Male; meta‐analysis; nonsyndromic cleft lip with or without cleft palate; polymorphism; Polymorphism, Genetic; 8q24; meta-analysis; nonsyndromic cleft lip with or without cleft palate; polymorphism; IRF6
• ISSN: 1542-0752; 1542-0760
• DOI: 10.1002/bdra.23540

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.