Association of WNT Pathway Genes With Nonsyndromic Cleft Lip With or Without Cleft Palate. (March 2018)

• Record Type: Journal Article
• Authors: Vijayan, V.; Ummer, R.; Weber, R.; Silva, R.; Letra, A.
• Is Part Of: Cleft palate-craniofacial journal. Volume 55:Number 3(2018)
• Page Start: 335
• Page End: 341
• Publication Date: 2018-03
• Subjects: WNT -- NSCL±P -- single-nucleotide polymorphism -- APC -- DVL2 -- GSK3B; Cleft palate -- Periodicals; Skull -- Abnormalities -- Periodicals; Cranial manipulation -- Periodicals; Skull -- Abnormalities -- Surgery -- Periodicals; Face -- Abnormalities -- Surgery -- Periodicals; Fente palatine -- Périodiques; Crâne -- Malformations -- Périodiques; Manipulation crânienne -- Périodiques; Crâne -- Malformations -- Chirurgie -- Périodiques; Face -- Malformations -- Chirurgie -- Périodiques; Cleft palate; Cranial manipulation; Face -- Abnormalities -- Surgery; Skull -- Abnormalities; Skull -- Abnormalities -- Surgery; Cleft Lip; Cleft Palate; Facial Bones -- abnormalities; Skull -- abnormalities; Periodicals; Periodicals; Periodicals; 617.522
• DOI: 10.1177/1055665617732782
• Languages: English
• ISSNs: 1055-6656

Abstract

Objective: Nonsyndromic cleft lip with or without cleft palate (NSCL±P) is a common craniofacial anomaly with multifactorial etiology. Evidence suggests that variations in WNT pathway genes contribute to an increased susceptibility to NSCL±P. The aim of this study was to investigate the association of AXIN1, APC, CTNNB1, DVL2, and GSK3β gene variants with NSCL±P in a case-control data set from Brazil. Patients: 471 individuals with NSCL±P and 504 unrelated control individuals of Caucasian ethnicity. Design: Twenty single-nucleotide polymorphisms (SNPs) in/nearby AXIN1, APC, CTNNB1, DVL2, and GSK3B genes were genotyped using Taqman chemistry in a Viia7 sequence detection instrument. Genotype, allele, and haplotype frequencies were compared among NSCL±P patients and controls using Fisher exact test, implemented in PLINK software. The level of significance was established at P ≤.002 under Bonferroni correction. In silico analysis of SNP function was assessed using MirSNP database. Results: Significant association was found between GSK3B rs13314595 genotypes and NSCL±P ( P = .0006). Additionally, nominal associations were found between DVL2 (rs35594616) and APC (rs448475) with NSCL±P ( P = .02 and P = .03, respectively). SNP haplotypes for GSK3B and APC genes showed nominal associations with NSCL±P ( P < .05). In silico analysis predicted that APC rs448475 harbors a binding site for the microRNA miR-617 and that the switch from a G allele to C allele enhances binding, whereas DVL2 rs35594616 did not appear to harbor microRNA-binding sites. Conclusion: This study shows for the first time the association between GSK3B and NSCL±P and confirms the role of additional WNT pathway genes as candidates for NSCL±P.