Studies with Wnt genes and nonsyndromic cleft lip and palate.
BACKGROUND
Clefts of the lip and/or palate (cleft lip/palate) are notable for their complex etiology. The WNT pathway regulates multiple developmental processes including craniofacial development and may play a role in cleft lip/palate and other defects of craniofacial development such as tooth agenesis. Variations in WNT genes have been recently associated with cleft lip/palate in humans. In addition, two WNT genes, Wnt3 and Wnt9B, are located in the clf1 cleft locus in mice.


METHODS
We investigated 13 SNPs located in Wnt3A, Wnt5A, Wnt8A, Wnt11, Wnt3, and Wnt9B genes for association with cleft lip/palate subphenotypes in 463 cleft cases and 303 unrelated controls. Genotyping of selected polymorphisms was carried out using Taqman assays. PLINK 1.06 software was used to test for differences in allele frequencies of each polymorphism between affected and unaffected individuals. Haplotype analysis was also performed.


RESULTS
Individuals carrying variant alleles in WNT3 presented an increased risk for cleft lip/palate (p = 0.0003; OR, 1.61; 95% CI, 1.29-2.02) in the population studied.


CONCLUSIONS
Our results continue to support a role for WNT genes in the pathogenesis of cleft lip/palate. Although much remains to be learned about the function of individual WNT genes during craniofacial development, additional studies should focus on the identification of potentially functional variants in these genes as contributors to human clefting. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.
Menezes
Renato
R
Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA 15261, USA.
Letra
Ariadne
A
Kim
Ana H
AH
Küchler
Erika C
EC
Day
Alicia
A
Tannure
Patricia N
PN
Gomes da Motta
Luise
L
Paiva
Katiucia B S
KB
Granjeiro
Jose M
JM
Vieira
Alexandre R
AR
D001938:Brazil; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics* / Q000473:pathology; D003744:Dental Enamel Hypoplasia / Q000473:pathology; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
C555507:WNT3 protein, human; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse