Deletion of LCE3C and LCE3B is a susceptibility factor for psoriatic arthritis: A study in Spanish and Italian populations and meta-analysis

Abstract

Objective. The LCE3C_LCE3B-del variant is associated with psoriasis and rheumatoid arthritis. Its role in psoriatic arthritis (PsA) is unclear, however, as shown by 3 recent studies with contradictory results. In order to investigate whether LCE3C_LCE3B-del constitutes a risk factor for PsA susceptibility, we first tested this variant in patients with PsA from Spanish and Italian populations and then performed a meta-analysis including the previous case-control studies.Methods. We genotyped LCE3C_LCE3B-del and its tag single-nucleotide polymorphism (SNP), rs4112788, in an original discovery cohort of 424 Italian patients with PsA and 450 unaffected control subjects. A Spanish replication cohort consisting of 225 patients with PsA and 469 control subjects was also genotyped. A meta-analysis considering 7,758 control subjects and 2,325 patients with PsA was also performed.Results. We observed a significant association between PsA and the LCE3C_LCE3B-del tag SNP in the Italian and Spanish cohorts, with an overall corrected P value of 0.00019 and a corresponding odds ratio of 1.35 (95% confidence interval 1.14-1.59). Stratified analyses by subphenotype indicated a stronger association for patients with oligoarticular disease. Meta-analysis including data from all previous published studies confirmed an association of PsA with the LCE3C_LCE3B-del tag SNP.Conclusion. LCE3C_LCE3B-del is a susceptibility factor for PsA, confirming the existence of a shared risk factor involving the epidermal skin barrier in autoimmune disorders.

Association of the Late Cornified Envelope-3 Genes with Psoriasis and Psoriatic Arthritis: A Systematic Review

“…There were significantly higher frequencies of the LCE3C_LCE3B-del allele and the C allele of rs4112788 in patients with PsA than controls in the original Italian cohort (Docampo et al, 2011). The frequency of the C (risk) allele of rs4112788 was also significantly different between PsA patients and controls in a replication of the Spanish cohort (Docampo et al, 2011).…”

“…There were significantly higher frequencies of the LCE3C_LCE3B-del allele and the C allele of rs4112788 in patients with PsA than controls in the original Italian cohort (Docampo et al, 2011). The frequency of the C (risk) allele of rs4112788 was also significantly different between PsA patients and controls in a replication of the Spanish cohort (Docampo et al, 2011). Variants in linkage disequilibrium with LCE3C_LCE3B-del were reported to be associated with increased susceptibility to PsA, providing evidence to support LCE3C_LCE3B-del as a risk factor for PsA (Bowes et al, 2010).…”

“…Numerous studies demonstrated that the LCE3 cluster genes are also associated with PsA (Bowes et al, 2010;Docampo et al, 2011). There were significantly higher frequencies of the LCE3C_LCE3B-del allele and the C allele of rs4112788 in patients with PsA than controls in the original Italian cohort (Docampo et al, 2011).…”

“…In order to clarify whether LCE3C_LCE3B-del is a susceptibility factor for PsA, a meta-analysis, including three previous studies in six different populations, was performed in 2011 (Docampo et al, 2011). The meta-analysis results suggested that LCE3C_LCE3B-del is a susceptibility factor for PsA considerably, and provided further evidence of the association of LCE3C_LCE3B-del with PsA.…”

Genetic Characteristics of Rheumatic Patients Developing Inflammatory Skin Lesions Induced by Biologic Therapy

“…4,[8][9][10] But what stands out is that all patients with ISL had at least one copy of the LCE3C LCE3B deleted alleles (absence of nondeleted homozygous individuals). In the general population, the frequency of non-deleted homozygotes is around 18% 4,9,10 and disruption of the skin barrier occurs in relation to the number of copies of LCE3C LCE3B, being undetectable in carriers of the homozygous deletion 4 and reduced in heterozygotes.…”