title: Human leukocyte antigen polymorphisms and personalized medicine for rheumatoid arthritis.
abstract: Human leukocyte antigen (HLA) polymorphisms are the most important genetic risk factors for rheumatoid arthritis (RA), a chronic systemic inflammatory disease of unknown etiology. Certain HLA-DRB1 alleles, known as shared epitope (SE) alleles because they have the same amino-acid sequence at positions 70-74, are associated with susceptibility to RA. A gene dosage effect is present for RA-predisposing SE alleles, and protective alleles show epistasis. An important role of amino-acid polymorphisms at positions 11 and 13 of the HLA-DRβ chain was also reported recently. Rheumatoid factor and anticitrullinated peptide antibodies are present in many RA patients. Similar to extra-articular manifestations, the presence of these autoantibodies is also associated with certain DRB1 alleles. Different frequencies of RA risk alleles in different ethnicities explain the varying prevalence of RA in different populations and suggest genetic heterogeneity of RA with regard to phenotype and population subsets. Some drug-induced hypersensitivity reactions due to disease-modifying antirheumatic drugs are also associated with HLA alleles. Understanding the role of HLA as the most important genetic factor relevant to RA susceptibility may help in determining its pathogenesis and pave the way to personalized medicine.
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan.
authors.forename: Hiroshi
authors.identifier: http://orcid.org/0000-0002-4022-0767
authors.initials: H
authors.lastname: Furukawa
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan.
authors.forename: Shomi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Department of Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan.|Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Fuchu, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashimoto
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D057285:Precision Medicine
chemical_list: D018501:Antirheumatic Agents; D006680:HLA Antigens