title: IRF6 gene variants in Central European patients with non-syndromic cleft lip with or without cleft palate.
abstract: Variants in the interferon regulatory factor 6 (IRF6) gene have repeatedly been associated with non-syndromic cleft lip with or without cleft palate (NSCL/P). A recent study has suggested that the functionally relevant variant rs642961 is the underlying cause of the observed associations. We genotyped rs642961 in our Central European case-control sample of 460 NSCL/P patients and 952 controls. In order to investigate whether other IRF6 variants contribute independently to the etiology of NSCL/P, we also genotyped the non-synonymous coding variant V274I (rs2235371) and five IRF6-haplotype tagging single nucleotide polymorphisms (SNPs). A highly significant result was observed for rs642961 (P = 1.44 x 10(-6)) in our sample. The odds ratio was 1.75 [95% confidence interval (CI): 1.38-2.22] for the heterozygous genotype and 1.94 (95% CI: 1.21-3.10) for the homozygous genotype, values that are similar to those reported in a previously published family-based study. Our results thus confirm the involvement of the IRF6 variant, rs642961, in the etiology of NSCL/P in the Central European population. We also found evidence suggestive of an independent protective effect of the coding variant V274I. In order to understand fully the genetic architecture of the IRF6 locus, it will be necessary to conduct additional SNP-based and resequencing studies using large samples of patients.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany. birnbaum@uni-bonn.de
authors.forename: Stefanie
authors.initials: S
authors.lastname: Birnbaum
authors.forename: Kerstin U
authors.initials: KU
authors.lastname: Ludwig
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Stefan
authors.initials: S
authors.lastname: Herms
authors.forename: Nilma A
authors.initials: NA
authors.lastname: de Assis
authors.forename: Amalia
authors.initials: A
authors.lastname: Diaz-Lacava
authors.forename: Sandra
authors.initials: S
authors.lastname: Barth
authors.forename: Carola
authors.initials: C
authors.lastname: Lauster
authors.forename: Gül
authors.initials: G
authors.lastname: Schmidt
authors.forename: Martin
authors.initials: M
authors.lastname: Scheer
authors.forename: Mitra
authors.initials: M
authors.lastname: Saffar
authors.forename: Markus
authors.initials: M
authors.lastname: Martini
authors.forename: Rudolf H
authors.initials: RH
authors.lastname: Reich
authors.forename: Franziska
authors.initials: F
authors.lastname: Schiefke
authors.forename: Alexander
authors.initials: A
authors.lastname: Hemprich
authors.forename: Simone
authors.initials: S
authors.lastname: Pötzsch
authors.forename: Bernd
authors.initials: B
authors.lastname: Pötzsch
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Per
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Michael
authors.initials: M
authors.lastname: Knapp
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Kramer
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
mesh_terms: D000225:Adenine; D000483:Alleles; D016022:Case-Control Studies; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003596:Cytosine; D005060:Europe; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006147:Guanine; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008297:Male; D016366:Open Reading Frames / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013941:Thymine; D014633:Valine / Q000235:genetics
chemical_list: C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D006147:Guanine; D003596:Cytosine; D014633:Valine; D000225:Adenine; D013941:Thymine