title: Protective effect of the HLA-DRB1*13:02 allele in Japanese rheumatoid arthritis patients.
abstract: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease. Certain HLA-DRB1 "shared-epitope" alleles are reported to be positively associated with increased RA susceptibility, whereas some of the other alleles may be negatively associated. However, studies on the latter are rare. Here, we focus on the protective effects of DRB1 alleles in Japanese RA patients in an association study. Relative predispositional effects (RPE) were analyzed by sequential elimination of carriers of each allele with the strongest association. The protective effects of DRB1 alleles were investigated in patients stratified according to whether they possessed anti-citrullinated peptide antibodies (ACPA). The DRB1*13:02 allele was found to be negatively associated with RA (P = 4.59×10(-10), corrected P (Pc) = 1.42×10(-8), odds ratio [OR] 0.42, 95% CI 0.32-0.55, P [RPE] = 1.27×10(-6)); the genotypes DRB1*04:05/*13:02 and *09:01/*13:02 were also negatively associated with RA. The protective effect of *13:02 was also present in ACPA-positive patients (P = 3.95×10(-8), Pc = 1.22×10(-6), OR 0.42, 95%CI 0.31-0.58) whereas *15:02 was negatively associated only with ACPA-negative RA (P = 8.87×10(-5), Pc = 0.0026, OR 0.26, 95%CI 0.12-0.56). Thus, this study identified a negative association of DRB1*13:02 with Japanese RA; our findings support the protective role of DRB1*13:02 in the pathogenesis of ACPA-positive RA.
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: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kawasaki
authors.affiliation: Department of Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan; Department of Rheumatology, Tokyo Metropolitan Tama Medical Center, Fuchu, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Rheumatology, Tokyo Metropolitan Tama Medical Center, Fuchu, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Sugii
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: Akiko
authors.initials: A
authors.lastname: Komiya
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
authors.affiliation: Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Rheumatology, Kumamoto Shinto General Hospital, Kumamoto, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Orthopedics/Rheumatology, Miyakonojo Hospital, National Hospital Organization, Miyakonojo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Saisho
authors.affiliation: Department of Internal Medicine, Nagoya Medical Center, National Hospital Organization, Nagoya, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Katayama
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Tsunoda
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sano
authors.affiliation: Clinical Research Center, Nagasaki Medical Center, National Hospital Organization, Omura, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.affiliation: Department of Rheumatology, Yokohama Minami Kyosai Hospital, Yokohama, Japan; Center for Rheumatic Diseases, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Suda
authors.affiliation: Department of Rheumatology, Yokohama Minami Kyosai Hospital, Yokohama, Japan.
authors.forename: Shouhei
authors.initials: S
authors.lastname: Nagaoka
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
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: D000328:Adult; D000483:Alleles; D000596:Amino Acids; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D044466:Asian People / Q000235:genetics*; D001323:Autoantibodies / Q000276:immunology; D016022:Case-Control Studies; D000939:Epitopes / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio
chemical_list: D000596:Amino Acids; D001323:Autoantibodies; D000939:Epitopes; D059811:HLA-DRB1 Chains