Association of WNT9B gene polymorphisms with nonsyndromic cleft lip with or without cleft palate in Brazilian nuclear families

摘要

Objective: Nonsyndromic cleft lip with or without cleft palate (NSCL±P) is a common craniofacial anomaly of complex etiology in people. WNT pathway genes have important roles during craniofacial development, and an association of WNT genes with NSCL±P has been demonstrated in different populations. The aim of this study was to evaluate the association between polymorphisms in WNT3 and WNT9B genes and CL/P in Brazilian families. Patients: Seventy nuclear families composed of an affected child and the child's unaffected parents were examined clinically. Saliva samples were collected for molecular analyses. Design: Three single nucleotide polymorphisms (SNPs) in the WNT3 gene and two in WNT9B were investigated in real-time polymerase chain reaction using TaqMan chemistry. The Family Based Association Test and the transmission disequilibrium test were used to verify the association between each marker allele and NSCL6P. The level of significance was established at P ≤ .01 after Bonferroni correction. Results: A positive association was detected between NSCL±P and SNP rs1530364 in the WNT9B gene. Haplotype analysis showed an association of WNT3 and WNT9B haplotypes. No association was detected between NSCL6P and individual SNPs in WNT3. Conclusion: Our study further supports the involvement of WNT9B as a cleft susceptibility gene in Brazilian families experiencing NSCL6P. Although additional studies are still necessary to unveil the exact mechanism by which WNT genes would contribute to NSCL6P, allelic polymorphisms in these genes and their interactions may partly explain the variance of individual susceptibility to NSCL6P.