Adult; Alleles; Arthritis, Psoriatic/genetics; Cornified Envelope Proline-Rich Proteins/genetics; European Continental Ancestry Group/genetics; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Italy; Male; Middle Aged; Polymorphism, Single Nucleotide; Spain
Abstract :
[en] 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.
Taylor, W., Gladman, D., Helliwell, P., Marchesoni, A., Mease, P., Mielants, H., Classification criteria for psoriatic arthritis: Development of new criteria from a large international study (2006) Arthritis and Rheumatism, 54 (8), pp. 2665-2673. , DOI 10.1002/art.21972
Bhalerao, J., Bowcock, A.M., The genetics of psoriasis: A complex disorder of the skin and immune system (1998) Human Molecular Genetics, 7 (10), pp. 1537-1545. , DOI 10.1093/hmg/7.10.1537
Myers, A., Kay, L.J., Lynch, S.A., Walker, D.J., Recurrence risk for psoriasis and psoriatic arthritis within sibships (2005) Rheumatology, 44 (6), pp. 773-776. , DOI 10.1093/rheumatology/keh589
Liu, Y., Helms, C., Liao, W., Zaba, L.C., Duan, S., Gardner, J., A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci (2008) PLoS Genet, 4, pp. e1000041
Gladman, D.D., Farewell, V.T., HLA studies in psoriatic arthritis: Current situation and future needs (2003) Journal of Rheumatology, 30 (1), pp. 4-6
De Cid, R., Riveira-Munoz, E., Zeeuwen, P.L., Robarge, J., Liao, W., Dannhauser, E.N., Deletion of the late cornified envelope LCE3C and LCE3B genes as a susceptibility factor for psoriasis (2009) Nat Genet, 41, pp. 211-215
Zhang, X.J., Huang, W., Yang, S., Sun, L.D., Zhang, F.Y., Zhu, Q.X., Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21 (2009) Nat Genet, 41, pp. 205-210
Huffmeier, U., Bergboer, J.G., Becker, T., Armour, J.A., Traupe, H., Estivil, X., Replication of LCE3C-LCE3B CNV as a risk factor for psoriasis and analysis of interaction with other genetic risk factors (2010) J Invest Dermatol, 130, pp. 979-984
Coto, E., Santos-Juanes, J., Coto-Segura, P., Diaz, M., Soto, J., Queiro, R., Mutation analysis of the LCE3B/LCE3C genes in psoriasis (2010) BMC Med Genet, 11, p. 45
Huffmeier, U., Estivill, X., Riveira-Munoz, E., Traupe, H., Wendler, J., Lohmann, J., Deletion of LCE3C and LCE3B genes at PSORS4 does not contribute to susceptibility to psoriatic arthritis in German patients (2010) Ann Rheum Dis, 69, pp. 876-878
Bowes, J., Flynn, E., Ho, P., Aly, B., Morgan, A.W., Marzo-Ortega, H., Variants in linkage disequilibrium with the late cornified envelope gene cluster deletion are associated with susceptibility to psoriatic arthritis (2010) Ann Rheum Dis, 69, pp. 2199-2203
Docampo, E., Rabionet, R., Riveira-Munoz, E., Escaramis, G., Julia, A., Marsal, S., Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumatoid arthritis (2010) Arthritis Rheum, 62, pp. 1246-1251
Bowcock, A.M., The genetics of psoriasis and autoimmunity (2005) Annual Review of Genomics and Human Genetics, 6, pp. 93-122. , DOI 10.1146/annurev.genom.6.080604.162324
Ioannidis, J.P., Patsopoulos, N.A., Evangelou, E., Heterogeneity in meta-analyses of genome-wide association investigations (2007) PLoS ONE, 2, pp. e841
Kane, D., Stafford, L., Bresnihan, B., FitzGerald, O., A classification study of clinical subsets in an inception cohort of early psoriatic peripheral arthritis - 'DIP or not DIP revisited' (2003) Rheumatology, 42 (12), pp. 1469-1476. , DOI 10.1093/rheumatology/keg445
Garrett, S., Jenkinson, T., Kennedy, L.G., Whitelock, H., Gaisford, P., Calin, A., A new approach to defining disease status in ankylosing spondylitis: The Bath Ankylosing Spondylitis Disease Activity Index (1994) J Rheumatol, 21, pp. 2286-2291
Calin, A., Garrett, S., Whitelock, H., Kennedy, L.G., O'Hea, J., Mallorie, P., A new approach to defining functional ability in ankylosing spondylitis: The development of the Bath Ankylosing Spondylitis Functional Index (1994) J Rheumatol, 21, pp. 2281-2285
Fries, J.F., Spitz, P., Kraines, R.G., Holman, H.R., Measurement of patient outcome in arthritis (1980) Arthritis and Rheumatism, 23 (2), pp. 137-145. , DOI 10.1002/art.1780230202
