Immunoprinting: various genes are associated with increased risk to develop rheumatoid arthritis in different groups of adult patients
| Autor: | Ekkehard D. Albert, O. Niwa, Cornelia Epplen, Jörg T. Epplen, J. E. Saal, H. Menninger, Maria Gomolka, E. M. Lemmel |
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| Rok vydání: | 1995 |
| Předmět: |
Genetic Markers
Male musculoskeletal diseases Genetic Linkage Sequence analysis Molecular Sequence Data Receptors Antigen T-Cell Locus (genetics) Human leukocyte antigen DNA Satellite Biology Arthritis Rheumatoid Antigens CD Risk Factors Drug Discovery Genetic predisposition medicine Humans Genetic Predisposition to Disease Genetic Testing Allele Alleles Genetics (clinical) Genetic association Genetics Polymorphism Genetic Base Sequence Tumor Necrosis Factor-alpha Interleukins Membrane Proteins Nuclear Proteins HLA-DR Antigens medicine.disease Rheumatoid arthritis Immunology Amino Acid Transport Systems Basic Molecular Medicine Microsatellite Female Carrier Proteins HLA-DRB1 Chains |
| Zdroj: | Journal of Molecular Medicine. 73:19-29 |
| ISSN: | 1432-1440 0946-2716 |
| Popis: | To identify genes that contribute to the manifestation of rheumatoid arthritis we performed association studies via microsatellite analyses of immunorelevant loci (HLA-DRB, 5 T cell receptor loci, TNFa IL1, IL2, IL5R and CD40L). A total of 183 patients and 275 healthy controls were typed in terms of HLA and grouped according to the known predisposing HLA-DRB1 genes (DRB1*04; relative risk approx. 5; DRB1*01, relative risk approx. 2; a third group carried neither allele). Microsatellite polymorphisms characterizing the TCRBV6S3, CD3D, IL1A, IL2, and IL5R genes did not show significant associations with rheumatoid arthritis, whereas TCRBV6S1, TCRBV6S7, TNFa, and CD40L genes may influence relative protection or risk in certain groups of patients. Analysis of a microsatellite marker adjacent to the transcription element alpha (TEA) in the T cell receptor alpha delta complex indicates that in the cohort carrying neither the DRB1*04 nor the DRB1*01 allele the relative risk to acquire rheumatoid arthritis is increased (13) or decreased (0.07), depending on the inherited microsatellite allele adjacent to the TEA locus. Sequence analysis of the closely linked TEA region from patients and controls revealed a novel dimorphism. Only the newly identified TEA allele leads to binding of a nuclear protein that may be involved in the regulated expression of the TCRDA genes. Subsequent typing of rheumatoid arthritis patients and controls revealed, however, that the association of the microsatellite marker is largely independent of the TEA allele, confirming incomplete linkage in the 2 kb region of the TCRDA locus. These results are discussed in the context of hot spots of recombination in this genomic region and other linked candidate sequences that predispose to develop rheumatoid arthritis. |
| Databáze: | OpenAIRE |
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