TGFB3 rs2300607 A/T polymorphism and nonsyndromic cleft lip and palate

INTRODUCTION: Non-syndromic cleft lip with or without cleft palate (NCLP) is a serious malformation. Asian populations, in general, have the highest prevalence of NCLP (at 1/500 at birth). The etiology is multifactorial involving multiple genetic and environmental factors. The transforming growth factor beta 3 (tgfb3) has an important role in morphogenesis of lip and palate. Two single nucleotide polymorphisms (SNP's) of the TGFB3 gene were found associated with NCLP in the Japanese population. We studied the rs2300607 A/T SNP located in the intron 1 of the TGFB3 gene in Guatemala. The Guatemalan population includes a high proportion of indigenous people of Asian origin.

MATERIAL AND METHODS: Blood specimens of 65 cases with NCLP and 96 controls were collected during Rotaplast medical missions to Guatemala City, Guatemala. The genotypes were established using polyacrylamide gel electrophoresis of rs2300607-specific DNA fragments amplified by PCR.

RESULTS: Proportions of genotypes were 53.73 % AA, 31.34 % AT, 14.93 % TT in cases and 48.96 % AA, 43.75 % AT, 7.29 % TT in controls. The A allele frequency was 0.69 for cases and 0.71 for controls. The T allele frequency was 0.31 for cases and 0.29 for controls. Haplotypes of rs2300607(A/T)/rs2268625(C/T) genotypes were ascertained in the same intron. The A/T and T/C haplotypes were more frequent in cases, while the A/C and T/T haplotypes were more frequent in controls. The differences between cases and controls were not statistically significant.

CONCLUSIONS: Tendencies to higher AA and TT genotype frequencies were found in cases. Also A/T and T/C rs23000607/rs2268625 haplotypes were found more frequently in cases. More cases and controls need to be evaluated to decide about statistical significance of these differences.

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