Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis
| Autor: | Xia Jiang, Henrik Källberg, Alejandro Balsa, Tore K Kvien, Paul I.W. de Bakker, Boel Brynedal, Nina A. Daha, Inge C. Olsen, Javier Gutierrez-Achury, René E. M. Toes, Bettina Kulle Andreassen, Fina A S Kurreeman, Javier Martín, Till Uhlig, Miguel A. González-Gay, Luis Rodriguez-Rodriguez, Marthe T. Maehlen, Benedicte A. Lie, Marte K. Viken, María Teruel, Lars Alfredsson, Alexandra Zhernakova |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
musculoskeletal diseases
Male medicine.medical_specialty SUSCEPTIBILITY LOCI Immunology European Continental Ancestry Group Single-nucleotide polymorphism Human leukocyte antigen Peptides Cyclic Risk Assessment White People General Biochemistry Genetics and Molecular Biology DISEASE PREDICT Arthritis Rheumatoid Rheumatology Rheumatoid Factor Risk Factors Internal medicine Rheumatoid medicine Immunology and Allergy Rheumatoid factor Humans COHORT Genetic Predisposition to Disease Allele CYCLIC CITRULLINATED PEPTIDE METAANALYSIS Alleles Autoantibodies Cyclic business.industry Arthritis Case-control study Autoantibody ASSOCIATION medicine.disease Connective tissue disease SHARED EPITOPE Rheumatoid arthritis Case-Control Studies ANTIBODIES Female business Peptides HLA-DRB1 Chains |
| Zdroj: | Annals of the Rheumatic Diseases, 74(4), 762-768. BMJ PUBLISHING GROUP Annals of the Rheumatic Diseases, 74(4), 762-768 Annals of the Rheumatic Diseases, 74(4), 762. BMJ Publishing Group |
| ISSN: | 0003-4967 |
| Popis: | Objective Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number of autoantibodies (none, one or two present).Method We calculated four GRSs in 4956 patients and 4983 controls from four European countries. All four scores contained data on 22 non-HLA-risk SNPs, and three scores also contained HLA-DRB1 genotypes but had different HLA typing resolution. Most patients had data on both rheumatoid factor (RF) and anti-citrullinated proteins antibodies (ACPA). The GRSs were standardised (std. GRS) to account for population heterogeneity. Discrimination between patients and controls was examined by receiveroperating characteristics curves, and the four std. GRSs were compared across subgroups according to autoantibody status.Results The std. GRS improved its discriminatory ability between patients and controls when HLA-DRB1 data of higher resolution were added to the combined score. Patients had higher mean std. GRS than controls (p=7.9x10(-156)), and this score was significantly higher in patients with autoantibodies (shown for both RF and ACPA). Mean std. GRS was also higher in those with two versus one autoantibody (p=3.7x10(-23)) but was similar in patients without autoantibodies and controls (p=0.12).Conclusions The GRS was associated with the number of autoantibodies and to both RF and ACPA positivity. ACPA play a more important role than RF with regards to the genetic risk profile, but stratification of patients according to both RF and ACPA may optimise future genetic studies. |
| Databáze: | OpenAIRE |
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