title: IFN-regulatory factor 5 gene variants interact with the class I MHC locus in the Swedish psoriasis population.
abstract: Psoriasis is a multifactorial disease of the skin with significant comorbidities of the musculoskeletal and cardiovascular system, which affects 2-3% of the Caucasian population. Failure to regulate prolonged T-helper 1-mediated inflammation is central to psoriasis and is a feature shared with other inflammatory diseases. IFNs are important initiators/regulators of inflammation that among other things can affect the expression of the main genetic determinant in psoriasis, namely HLA-C. Externally administered IFN-alpha, as in patients treated for viral infections, and IFN-alpha produced by plasmacytoid dendritic cells is a known trigger of psoriasis. IFNgamma is characteristically increased in psoriasis lesions. Expression of IFNs is controlled by factors such as IFN-regulatory factor 5 (IRF5) whose polymorphic haplotypes were recently found to associate with increased risk of systemic lupus erythematosus (SLE). The hypothesis underlying this study was that polymorphisms in the IRF5 gene contribute to inadequate control of inflammation in psoriasis. This hypothesis was tested by comparing the distribution of genotypes and haplotypes at IRF5 derived from genotyping single-nucleotide polymorphisms (SNPs) rs2004640, rs2070197, rs10954213, and rs2280714 in psoriasis patients and population-matched controls from the Stockholm Psoriasis Cohort. Polymorphisms at IRF5 did not associate with psoriasis per se; however, an interaction with class I major histocompatibility complex (MHC) genes was found.
authors.affiliation: Department of Medicine, Molecular Unit of Dermatology and Venereology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. Fabio.Sanchez@ki.se
authors.forename: Fabio O
authors.initials: FO
authors.lastname: Sánchez
authors.forename: M V Prasad
authors.initials: MV
authors.lastname: Linga Reddy
authors.forename: Lotus
authors.initials: L
authors.lastname: Mallbris
authors.forename: Kazuko
authors.initials: K
authors.lastname: Sakuraba
authors.forename: Mona
authors.initials: M
authors.lastname: Ståhle
authors.forename: Marta E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D005260:Female; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D059951:HLA-G Antigens; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology
chemical_list: D006680:HLA Antigens; D015236:HLA-C Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors