title: Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients.
abstract: Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD.
authors.affiliation: Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Paradowska-Gorycka
authors.affiliation: Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Stypińska
authors.affiliation: Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Olesińska
authors.affiliation: Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Felis-Giemza
authors.affiliation: Department of Epidemiology and Health Promotion, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Mańczak
authors.affiliation: Department of Internal Medicine, Connective Tissue Disease and Geriatrics, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Czuszynska
authors.affiliation: Department of Internal Medicine, Connective Tissue Disease and Geriatrics, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Zdrojewski
authors.affiliation: DNA Research Center, Poznan, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Wojciechowicz
authors.affiliation: Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Jurkowska
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D003882:Dermatomyositis / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008947:Mixed Connective Tissue Disease / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011044:Poland; D012042:Registries; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000276:immunology; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D001323:Autoantibodies; D059811:HLA-DRB1 Chains; D017412:Ribonucleoprotein, U1 Small Nuclear
keywords: HLA; association study; genetics; humans; mixed connective tissue disease