Cleft lip and palate anomaly and TGFB3 rs2268625 C/T polymorphism

INTRODUCTION: Non-syndromic cleft lip with or without cleft palate (NCLP) is a common craniofacial malformation with a complex genetic component of its multifactorial etiology. The transforming growth factor beta 3 (tgfb3) is involved in morphogenesis of lip and palate. Recently, two single nucleotide polymorphisms (SNP's) of the TGFB3 gene were found to be associated with NCLP in the Japanese population. In general, Asian populations have the highest prevalence of NCLP, around 1/500 at birth. We studied the rs2268625 C/T SNP located in intron 1 of the TGFB3 gene in the Guatemalan population that includes a high proportion of indigenous people of Asian origin.

MATERIAL AND METHODS: Venous blood was collected from 85 cases with NCLP and 72 controls during Rotaplast medical missions to Guatemala City, Guatemala. DNA was isolated from dried blood spots. Genotypes were established by sequencing of rs2268625-specific DNA fragments amplified by PCR.

RESULTS: Proportions of genotypes were 8.24 % CC, 40.00 % CT, 51.76 % TT in cases and 9.73 % CC, 44.44 % CT, 45.83 % TT in controls. The C allele frequency was 0.28 for cases and 0.32 for controls. The T allele frequency was 0.72 for cases and 0.68 for controls. Combinations of rs2300607(A/T)/rs2268625(C/T) genotypes were ascertained in the same intron. The AA/TT combination was more frequent in cases, while the AT/CT combination was more frequent in controls. The differences between cases and controls were not statistically significant.

CONCLUSIONS: Slightly higher T allele and TT genotype frequencies were found in cases. Also AA(rs23000607)/TT(rs2268625) genotype combination was found more frequently in cases. Additional cases and controls need to be evaluated to show, whether the differences are statistically significant.

ACKNOWLEDGEMENTS: The fieldwork for this study was supported by Rotaplast International, Inc.