Dissecting the Genetic Complexity of the Association between Human Leukocyte Antigens and Rheumatoid Arthritis
| Autor: | Henry A. Erlich, Timothy W. Behrens, Peter K. Gregersen, Teodorica L. Bugawan, Christopher I. Amos, Aarti Damle, Robert Lundsten, Wei V. Chen, Annette Lee, Ann B. Begovich, Damini Jawaheer, Robert R. Graham, Michael F. Seldin, Wentian Li, Joanita Monteiro, Lindsey A. Criswell, Houman Khalili, James T. Elder, Xiangli Xiao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
musculoskeletal diseases
Linkage disequilibrium Entropy Human leukocyte antigen Biology Major histocompatibility complex Genetic determinism Linkage Disequilibrium Arthritis Rheumatoid 03 medical and health sciences 0302 clinical medicine HLA Antigens Genetics Humans Genetics(clinical) Genetic Predisposition to Disease Allele Genetics (clinical) HLA Complex Alleles 030304 developmental biology 030203 arthritis & rheumatology 0303 health sciences Haplotype Articles HLA-DR Antigens 3. Good health Histocompatibility Pedigree Haplotypes Immunology biology.protein Software HLA-DRB1 Chains |
| Popis: | Rheumatoid arthritis (RA) is an inflammatory disease with a complex genetic component. An association between RA and the human leukocyte antigen (HLA) complex has long been observed in many different populations, and most studies have focused on a direct role for the HLA-DRB1 “shared epitope” in disease susceptibility. We have performed an extensive haplotype analysis, using 54 markers distributed across the entire HLA complex, in a set of 469 multicase families with RA. The results show that, in addition to associations with the DRB1 alleles, at least two additional genetic effects are present within the major histocompatibility complex. One of these lies within a 497-kb region in the central portion of the HLA complex, an interval that excludes DRB1. This genetic risk factor is present on a segment of a highly conserved ancestral A1-B8-DRB1*03 (8.1) haplotype. Additional risk genes may also be present in the HLA class I region in a subset of DRB1*0404 haplotypes. These data emphasize the importance of defining haplotypes when trying to understand the HLA associations with disease, and they clearly demonstrate that such associations with RA are complex and cannot be completely explained by the DRB1 locus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|