title: Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors.
abstract: Recently, a deletion of two late cornified envelope (LCE) genes within the epidermal differentiation complex on chromosome 1 was shown to be overrepresented in 1,426 psoriasis vulgaris (PsV) patients of European ancestry. In this study, we report a confirmation of this finding in 1,354 PsV patients and 937 control individuals of German origin. We found an allele frequency of the deletion of 70.9% in PsV patients and of 64.9% in control individuals (chi(2)=17.44, P=2.97 x 10(-5), odds ratio (95% confidence interval)=1.31 (1.15-1.48)). The overall copy number of the two LCE genes had no influence on the age of onset, but we observed a dosage effect at the genotype level. There was no evidence of statistically significant interaction with copy number of the beta-defensin cluster on 8p23.1 or with an IL-23R pathway variant in a combined data set of German and Dutch individuals, whereas evidence for interaction with the PSORS1 risk allele in German individuals was marginal and did not remain significant after correction for multiple testing. Our study confirms the recently published finding that the deletion of the two LCE genes is a susceptibility factor for PsV with dosage effect, while, because of power limitation, no final conclusion regarding interaction with other PsV risk factors can be made at this stage.
authors.affiliation: Institute of Human Genetics, University Hospital Erlangen, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hüffmeier
authors.forename: Judith G M
authors.initials: JG
authors.lastname: Bergboer
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: John A
authors.initials: JA
authors.lastname: Armour
authors.forename: Heiko
authors.initials: H
authors.lastname: Traupe
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Eva
authors.initials: E
authors.lastname: Riveira-Munoz
authors.forename: Rotraut
authors.initials: R
authors.lastname: Mössner
authors.forename: Kristian
authors.initials: K
authors.lastname: Reich
authors.forename: Werner
authors.initials: W
authors.lastname: Kurrat
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Joost
authors.initials: J
authors.lastname: Schalkwijk
authors.forename: Patrick L J M
authors.initials: PL
authors.lastname: Zeeuwen
authors.forename: André
authors.initials: A
authors.lastname: Reis
mesh_terms: D000328:Adult; D017668:Age of Onset; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics*; D017353:Gene Deletion; D018628:Gene Dosage; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005858:Germany / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D011565:Psoriasis / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000706:statistics & numerical data*; D023083:beta-Defensins / Q000235:genetics
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; C524768:LCE3C protein, human; C484393:PSORS1C1 protein, human; D011506:Proteins; D023083:beta-Defensins