Association of TGFB3 and FGFs gene polymorphisms with cleft lip with or without cleft palate a systematic review

Objectives: The objective of this study was to conduct a systematic review of the possible association between transforming growth factor B3 (TGFB3) and fibroblast growth factors (FGFs) gene polymorphisms and nonsyndromic cleft lip with or without cleft palate (NSCL/P). Material and Methods: Two reviewers independently screened studies by examining all titles and abstracts. Studies were included if they met the following criteria: The outcome of interest was NSCL/P; the polymorphisms studied were TGFB3 and FGF; they presented sufficient data, that is, allele/genotype frequency between cases and controls; or their odds ratio with 95% confidence interval. Study quality was independently assessed by a risk of bias assessment for genetic association studies. Results: Based on the inclusion criteria, we have selected a total of six articles (four for TGFB and two for FGF). Particularly for the TGFB gene, we have found significant results in exon 4 in the variant g.15812T>G, and in the single-nucleotide polymorphisms rs2300607 A/T, in the distribution between cases and controls. On the other hand, for the FGF gene, we observed a statistically significant in the genotype rs34010 CA. Conclusion: None of the genetic variations that show the association is verified in different populations; therefore, there is not enough scientific validation regarding the association between TGFB and FGF polymorphism and NSCL/P. The findings of the different studies suggest the need for further investigations with samples composed of a larger number of individuals in different populations, which should be performed with all the standards for genetic studies, thus allowing an understanding of the molecular basis of the disease.