Association of WNT9B Gene Polymorphisms With Nonsyndromic Cleft Lip With or Without Cleft Palate in Brazilian Nuclear Families.
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.


METHODS
Seventy nuclear families composed of an affected child and the child's unaffected parents were examined clinically. Saliva samples were collected for molecular analyses.


METHODS
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 NSCL±P. 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 NSCL±P and individual SNPs in WNT3.


CONCLUSIONS
Our study further supports the involvement of WNT9B as a cleft susceptibility gene in Brazilian families experiencing NSCL±P. Although additional studies are still necessary to unveil the exact mechanism by which WNT genes would contribute to NSCL±P, allelic polymorphisms in these genes and their interactions may partly explain the variance of individual susceptibility to NSCL±P.
Clarissa
C
Fontoura
Renato M
RM
Silva
José M
JM
Granjeiro
Ariadne
A
Letra
D000293:Adolescent; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D051153:Wnt Proteins / Q000235:genetics*; D060508:Wnt3 Protein / Q000235:genetics
C555507:WNT3 protein, human; C449090:WNT9B protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein
association; cleft lip/palate; genetic polymorphisms