Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors

Ulrike Hüffmeier, Judith G.M. Bergboer, Tim Becker, John A. Armour, Heiko Traupe, Xavier P. Estivill, Eva Riveira-Munoz, Rotraut Mössner, Kristian Reich, Werner Kurrat, Thomas F. Wienker, Joost Schalkwijk, Patrick L.J.M. Zeeuwen, André Reis

Research output: Contribution to journalArticle

55 Citations (Scopus)

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 (X2= 17.44, P2.97 × 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 Β-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.

Original languageEnglish
Pages (from-to)979-984
Number of pages6
JournalJournal of Investigative Dermatology
Volume130
Issue number4
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

Fingerprint

Psoriasis
Statistical Factor Analysis
Genes
Defensins
Chromosomes
Chromosomes, Human, Pair 1
Age of Onset
Gene Frequency
Testing
Alleles
Odds Ratio
Genotype
Confidence Intervals

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors. / Hüffmeier, Ulrike; Bergboer, Judith G.M.; Becker, Tim; Armour, John A.; Traupe, Heiko; Estivill, Xavier P.; Riveira-Munoz, Eva; Mössner, Rotraut; Reich, Kristian; Kurrat, Werner; Wienker, Thomas F.; Schalkwijk, Joost; Zeeuwen, Patrick L.J.M.; Reis, André.

In: Journal of Investigative Dermatology, Vol. 130, No. 4, 04.2010, p. 979-984.

Research output: Contribution to journalArticle

Hüffmeier, U, Bergboer, JGM, Becker, T, Armour, JA, Traupe, H, Estivill, XP, Riveira-Munoz, E, Mössner, R, Reich, K, Kurrat, W, Wienker, TF, Schalkwijk, J, Zeeuwen, PLJM & Reis, A 2010, 'Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors', Journal of Investigative Dermatology, vol. 130, no. 4, pp. 979-984. https://doi.org/10.1038/jid.2009.385
Hüffmeier, Ulrike ; Bergboer, Judith G.M. ; Becker, Tim ; Armour, John A. ; Traupe, Heiko ; Estivill, Xavier P. ; Riveira-Munoz, Eva ; Mössner, Rotraut ; Reich, Kristian ; Kurrat, Werner ; Wienker, Thomas F. ; Schalkwijk, Joost ; Zeeuwen, Patrick L.J.M. ; Reis, André. / Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors. In: Journal of Investigative Dermatology. 2010 ; Vol. 130, No. 4. pp. 979-984.
@article{d50cb10469004a2b867ad7951c4b53d7,
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 (X2= 17.44, P2.97 × 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 Β-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.",
author = "Ulrike H{\"u}ffmeier and Bergboer, {Judith G.M.} and Tim Becker and Armour, {John A.} and Heiko Traupe and Estivill, {Xavier P.} and Eva Riveira-Munoz and Rotraut M{\"o}ssner and Kristian Reich and Werner Kurrat and Wienker, {Thomas F.} and Joost Schalkwijk and Zeeuwen, {Patrick L.J.M.} and Andr{\'e} Reis",
year = "2010",
month = "4",
doi = "10.1038/jid.2009.385",
language = "English",
volume = "130",
pages = "979--984",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors

AU - Hüffmeier, Ulrike

AU - Bergboer, Judith G.M.

AU - Becker, Tim

AU - Armour, John A.

AU - Traupe, Heiko

AU - Estivill, Xavier P.

AU - Riveira-Munoz, Eva

AU - Mössner, Rotraut

AU - Reich, Kristian

AU - Kurrat, Werner

AU - Wienker, Thomas F.

AU - Schalkwijk, Joost

AU - Zeeuwen, Patrick L.J.M.

AU - Reis, André

PY - 2010/4

Y1 - 2010/4

N2 - 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 (X2= 17.44, P2.97 × 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 Β-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.

AB - 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 (X2= 17.44, P2.97 × 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 Β-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.

UR - http://www.scopus.com/inward/record.url?scp=77949542167&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949542167&partnerID=8YFLogxK

U2 - 10.1038/jid.2009.385

DO - 10.1038/jid.2009.385

M3 - Article

VL - 130

SP - 979

EP - 984

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 4

ER -