A Meta-analysis Of The Relationship Between Four Polymorphisms And Non-syndromic Cleft Lip With Or Without Cleft Palate

Objective Recently, searching the relationship between single nucleotide polymorphisms and cleft lip with or without cleft palate is immense. The main purpose of this study was to investigate the correlation of four single nucleotide polymorphisms, rs2235371 and rs642961 in Interferon Regulatory Factor6(IRF6), rs987525 in 8q24 as well as rs7078160 in 10q25 with nonsyndromic cleft lip with our without palate. In some literatures, these four polymorphisms were considered to be risk factors against nonsyndromic cleft lip with our without palate. In contrast, other documents held the opposite views. The inconsistent results of the studies may be mainly originated from the limited samples recruited. Increasing the sample size is a reliable way to reduce the sampling error. And Meta analysis is based on the thought of synthesizing studies with small homogeneity and increasing the sample, to make the synthetic result can be more close to the truth. In order to find out the relation between these four polymorphisms and the nonsyndromic cleft lip with our without palate, we conducted a meta analysis, to include all the studies met our criteria as much as possible.Methods Three database, MEDLINE(via Pub Med), EMBASE(via Ovid) and CENTRAL(via Cochranelibrary), were employed to search the aimed papers according to the inclusion criteria. The authors independently judged which literatures can be eligible in the Meta analysis, and the consistency was calculated by the Kappa value. Two authors collected information from the included literatures independently, and the inconsistence were settled throuth discuss or by a third author. Stata 12.0 software was used to perform heterogeneity test, publication bias, sensitivity analysis and to draw the forest as well as funnel figure. Indifference-level was P < 0.05. P > 0.05 indicated the heterogeneity between studies was small, then the fixed effect model is used to synthesize statistics, conversely with the random effects model. Newcastle- OttawaScale was employed to assess bias risk of the included studies. And a high risk of bias study was with four stars, a moderate risk of bias study with 4 ~ 6 stars, a low risk of bias study with more than 7 stars.Results The four Meta-analysises totally contained 25 originally eligible researches, out of these, 10 for rs2235371, 7 for rs642961, 10 for rs987525, 7 for rs7078160. Newcastle-Ottawa scale was used to measure the risk of bias of studies. The results showed that, 16 had low risk of bias, 9 had moderate risk of bias. P value of heterogeneity test was 0.12, 0.30, 0.09, 0.05 respectively. So the fixed effect model was used to synthesize statistical results. The results showed that rs2235371(A allele vs G allele) could decrease risk of nonsyndromic cleft lip with or without cleft palate OR 0.81,95%CI 0.71~0.92), while rs642961(A allele vs G allele), rs987525(A allele vs C allele), rs7078160(A allele vs C allele) can increase 103% 、 75% 、 32% risk against nonsyndromic cleft lip with or without cleft palate(OR 2.03,95%CI 1.85~2.22;OR 1.75,95%CI 1.61~1.90;OR 1.32,95%CI 1.18~1.47 respectively. No significant publication bias was existed. Sensitivity analysis results remained stable.Conclusion Overall, rs2235371 may be seen as a preventive factor against the nonsyndromic cleft lip with our without palate, while rs642961, rs987525 and rs7078160 as risks.