title: ERAP1 and ERAP2 Gene Variations Influence the Risk of Psoriatic Arthritis in Romanian Population.
abstract: Psoriatic arthritis (PsA) is a chronic inflammatory disorder that belongs to the group of spondyloarthritis (SpA). It was found that single nucleotide polymorphisms (SNPs) of endoplasmic reticulum aminopeptidase (ERAP1 and ERAP2) genes influence the risk of ankylosing spondylitis, the most common form of SpA and the risk of psoriasis. Our purpose was to investigate the possible association of ERAP1 and ERAP2 gene SNPs with psoriatic arthritis susceptibility in Romanian population. Subsequent analyses included patients' subgroups according to HLA-B27 status. Psoriatic arthritis patients (N = 98) and random healthy controls (N = 139) were genotyped for ERAP1/2 genes SNPs rs30187, rs27044, rs2910686, and rs2248374 by TaqMan Allelic Discrimination Assays. An additional control group (N = 108; 100% HLA-B27 positive) was used for subsequent analyses. The results showed the association of rs2248374 SNP of ERAP2 gene with the risk of PsA, especially for HLA-B27 negative disease (p = 0.02; OR 1.59). ERAP2 haplotype GT (rs2248374/rs2910686) was significantly under-represented in PsA patients than in controls (43 vs. 55%; p = 0.02). The analysis of ERAP1 SNPs in HLA-B27 positive controls and PsA subgroup showed strong evidence of association for rs30187 (p = 0.005; OR 2.73) and for CC rs30187/rs27044 haplotype (47% in patients vs. 70.5% in controls; p = 0.006). In conclusion, we found a significant association of ERAP2 with PsA and HLA-B27 negative PsA, while ERAP1 association was restricted only to HLA-B27 positive disease. To our knowledge, this is the first study that investigated ERAP2 polymorphisms in relation to PsA susceptibility.
authors.affiliation: Department of Immunology and Pathophysiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. oliviapopa@yahoo.com.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Popa
authors.affiliation: Department of Immunology and Pathophysiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Marius
authors.initials: M
authors.lastname: Cherciu
authors.affiliation: Department of Immunology and Pathophysiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Laura I
authors.initials: LI
authors.lastname: Cherciu
authors.affiliation: "Prof. Dr. C. T. Nicolau" National Institute of Blood Transfusion, Bucharest, Romania.
authors.forename: Monica I
authors.initials: MI
authors.lastname: Dutescu
authors.affiliation: Department of Rheumatology, Faculty of Medicine, "I. Cantacuzino" Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Mihai
authors.initials: M
authors.lastname: Bojinca
authors.affiliation: Department of Rheumatology, Faculty of Medicine, Sf. Maria Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Violeta
authors.initials: V
authors.lastname: Bojinca
authors.affiliation: Department of Immunology and Pathophysiology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Constantin
authors.initials: C
authors.lastname: Bara
authors.affiliation: Molecular Biology Department, Grigore Antipa National Museum of Natural History, Bucharest, Romania.
authors.forename: Luis O
authors.initials: LO
authors.lastname: Popa
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000626:Aminopeptidases / Q000235:genetics*; D015535:Arthritis, Psoriatic / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012383:Romania; D013167:Spondylitis, Ankylosing / Q000235:genetics*
chemical_list: D015796:HLA-B27 Antigen; D015778:Minor Histocompatibility Antigens; D000626:Aminopeptidases; C464841:ERAP1 protein, human; C503944:ERAP2 protein, human
keywords: ERAP1; ERAP2; Haplotype; Psoriatic arthritis; Single nucleotide polymorphism