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.

Pathogenesis of Atopic Dermatitis and Psoriasis: Focus on the Epidermal Differentiation Complex~!2009-11-06~!2009-12-10~!2010-04-23~!

“…These results have been replicated in a German cohort [34]. In addition, in an independent genome wide association study of a large Chinese cohort, single nucleotide polymorphisms (SNPs) in strong LD with the LCE3B/C deletion were identified as risk factors for psoriasis [35].…”

Variants in MHC, LCE and IL12B have epistatic effects on psoriasis risk in Chinese population

“…Interaction studies among parts of these genes have also been conducted in large sample [16,[19][20][21]. As GWA studies have produced a large amount of data, further study on gene-gene interaction and multimarker association would be important for elucidating the biological and biochemical pathways that underline disease [22].…”

Psoriasis Risk Genes of the Late Cornified Envelope-3 Group Are Distinctly Expressed Compared with Genes of Other LCE Groups

“…5 This association has been widely replicated in cohorts of European and Asian origin. 6,7 The LCE genes are located on chromosome 1q21 in a region called the epidermal differentiation complex. 8 This region is enriched for genes expressed during epidermal differentiation including loricrin, involucrin, filaggrin, the small proline-rich protein genes, and the LCE genes.…”