IRF6 gene variants in Central European patients with non-syndromic cleft lip with or without cleft palate.
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.
Birnbaum
Stefanie
S
Institute of Human Genetics, University of Bonn, Bonn, Germany. birnbaum@uni-bonn.de
Ludwig
Kerstin U
KU
Reutter
Heiko
H
Herms
Stefan
S
de Assis
Nilma A
NA
Diaz-Lacava
Amalia
A
Barth
Sandra
S
Lauster
Carola
C
Schmidt
Gül
G
Scheer
Martin
M
Saffar
Mitra
M
Martini
Markus
M
Reich
Rudolf H
RH
Schiefke
Franziska
F
Hemprich
Alexander
A
Pötzsch
Simone
S
Pötzsch
Bernd
B
Wienker
Thomas F
TF
Hoffmann
Per
P
Knapp
Michael
M
Kramer
Franz-Josef
FJ
Nöthen
Markus M
MM
Mangold
Elisabeth
E
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
C109803:IRF6 protein, human; D050835:Interferon Regulatory Factors; D006147:Guanine; D003596:Cytosine; D014633:Valine; D000225:Adenine; D013941:Thymine