Association of TGFβ3 variants with Nonsyndromic Cleft Lip and Palate in Guatemalan Population.

Abstract

Introduction: Nonsyndromic cleft lip with or without cleft palate (NCL/P) is a common orofacial anomaly with a multifactorial etiology. The genetic component of NCL/P etiology is complex with multiple genes involved. The transforming growth factor beta 3 (TFGβ3) is among the strong susceptibility genes that have been shown to be involved in morphogenesis of lip and palate. Materials and Methods: Case-control study design was used in this study. Cases (n=237) were patients affected with NCL/P identified at the Roosevelt Hospital in Guatemala City, Guatemala. Controls (n=168) were individuals with no history of NCL/P from the same hospital. Genotypes were established by PCR and PAGE for TGFβ3 rs2300607 A/T SNP and by PCR and sequencing for TGFβ3 rs2268625 C/T SNP. Results: For rs23000607A/T, a proportion of TT homozygotes was significantly higher (p=0.029) in cases than in controls (13.92% vs 5.36%). T allele frequency was 0.340 in cases and 0.274 in controls. Also for rs2268625 C/T, a significantly higher proportion of TT homozygotes was found among cases than among controls (p=0.041; 54.0% vs. 48.98%). Frequency of mutated T allele was 0.744 in cases and 0.694 in controls. Conclusion: The results of our study showed for the first time the association between TGFβ3 rs2268625 C/T polymorphism and NCL/P and confirmed for Guatemalan population the association between TGFβ3 rs2300607 A/T polymorphism and NCL/P found by Ichikawa in Japanese by Ichikava et al. in 2006. Thus, our findings suggest that rs2268625 C/T and rs2300607 A/T mutations in the TGFβ3 gene are associated with NCL/P in Guatemalan population.