| Affiliation: | 1. Institute of Human Genetics, University of Bonn, Bonn;2. Department of Genomics, Life and Brain Center, University of Bonn, Bonn;3. Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn;4. Department of Cleft Lip and Cleft Palate Surgery, Humboldt University, Berlin;5. Department of Oral and Maxillo‐Facial Surgery, University of Cologne, K?ln;6. Department of Orthodontics, University of Cologne, K?ln;7. Department of Oral and Maxillo‐Facial‐Plastic Surgery, University of Bonn, Bonn;8. Department of Oral and Maxillo‐Facial Surgery, University of Leipzig, Leipzig;9. Monitoring of Congenital Malformations Saxony Anhalt, University of Magdeburg, Magdeburg;10. Institute of Experimental Hematology and Transfusion Medicine, University of Bonn, Bonn;11. Department of Oral and Maxillo‐Facial Surgery, University of G?ttingen, G?ttingen, Germany |
| 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 × 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. |
