title: Association of DVL2 and AXIN2 gene polymorphisms with cleft lip with or without cleft palate in a Polish population.
abstract: BACKGROUND
  Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital anomalies, with a complex and still not fully understood etiology. Given the important role of the Wnt/β-catenin pathway during craniofacial development, we decided to test the hypothesis that common polymorphic variants of the genes encoding crucial components of this signaling pathway might contribute to the risk of NSCL/P in the Polish population.
  
  
  METHODS
  A set of 19 single nucleotide polymorphisms (SNPs) in the APC, AXIN1, AXIN2, CTNNB1, DVL2, and GSK-3β genes were analyzed using restriction fragment length polymorphism and high-resolution melting curve methods in a group of 280 patients with NSCL/P and a properly matched control group (n = 330).
  
  
  RESULTS
  Both single-marker and haplotype analyses showed an association between SNPs in the DVL2 gene and the risk for NSCL/P. The strongest association was found under an overdominant model for the rs35594616 variant located in the exonic sequence of DVL2 (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.37-2.62; p < 0.0001). Moreover, the gene-gene interaction analysis revealed a significant epistatic interaction between DVL2 gene SNPs in the susceptibility to orofacial clefts. Borderline association with a decreased risk of NSCL/P was also observed for the AXIN2 rs3923087 variant (dominant model OR, 0.69; 95% CI, 0.50-0.95; p = 0.03).
  
  
  CONCLUSIONS
  This study suggests that polymorphic variants of the Wnt/β-catenin pathway genes have a role in the susceptibility to orofacial clefts. The DVL2 and AXIN2 genes might be candidate genes for this craniofacial anomaly in the Polish population. Birth Defects Research (Part A), 2012.
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland. amostowska@wp.pl
authors.forename: Adrianna
authors.initials: A
authors.lastname: Mostowska
authors.forename: Kamil K
authors.initials: KK
authors.lastname: Hozyasz
authors.forename: Piotr
authors.initials: P
authors.lastname: Wójcicki
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lasota
authors.forename: Izabella
authors.initials: I
authors.lastname: Dunin-Wilczyńska
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodziński
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D060466:Axin Protein / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D000072261:Dishevelled Proteins; D005260:Female; D015870:Gene Expression; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D044465:White People; D060449:Wnt Signaling Pathway
chemical_list: C491761:AXIN2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; D010750:Phosphoproteins