title: An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population: effects of *09:01 allele on disease phenotypes.
abstract: Objective. To re-evaluate the roles of HLA-DRB1 alleles in susceptibility to SLE and RA and their effects on autoantibody status in large-scale Japanese cohorts. Methods. A total of 656 SLE, 2410 RA and 911 control subjects, who were all Japanese, were genotyped for HLA-DRB1 alleles using sequence-specific oligonucleotide probes. The association of alleles with disease susceptibility was tested by logistic regression analysis and by the relative predispositional effect method. The association with autoantibody status was examined by the standard χ(2) test. Results. HLA-DRB1*15:01, *09:01, *08:02 and *04:01 were significantly associated with SLE susceptibility, while shared epitope (SE) alleles and DRB1*09:01 were associated with RA susceptibility. The compound heterozygote of DRB1*09:01/*15:01 conferred an increased risk for SLE compared with the homozygotes for DRB1*09:01 and *15:01 and was associated with earlier onset of disease, whereas the compound effect of DRB1-SE/*09:01 was not clear in RA. DRB1*09:01 was significantly associated with the appearance of anti-Sm antibody in SLE as well as ACPA in RA, while protectively associated with anti-dsDNA antibody in SLE. No significant interaction was observed between DRB1*09:01 and smoking status for the appearance of ACPA, unlike that observed in SE alleles in RA. Conclusion. We identified HLA-DRB1 alleles associated with SLE and RA in a Japanese population and demonstrated a shared susceptibility of DRB1*09:01 between the diseases as well as its effect on autoantibody production.
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Kenichi
authors: K
authors: Shimane
authors: Yuta
authors: Y
authors: Kochi
authors: Akari
authors: A
authors: Suzuki
authors: Yukinori
authors: Y
authors: Okada
authors: Tomonori
authors: T
authors: Ishii
authors: Tetsuya
authors: T
authors: Horita
authors: Kazuyoshi
authors: K
authors: Saito
authors: Akiko
authors: A
authors: Okamoto
authors: Norihiro
authors: N
authors: Nishimoto
authors: Keiko
authors: K
authors: Myouzen
authors: Michiaki
authors: M
authors: Kubo
authors: Michito
authors: M
authors: Hirakata
authors: Takayuki
authors: T
authors: Sumida
authors: Yoshinari
authors: Y
authors: Takasaki
authors: Ryo
authors: R
authors: Yamada
authors: Yusuke
authors: Y
authors: Nakamura
authors: Naoyuki
authors: N
authors: Kamatani
authors: Kazuhiko
authors: K
authors: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D044466:Asian People / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D059811:HLA-DRB1 Chains; C487381:HLA-DRB1*09:01 antigen
keywords: Asian population; association study; autoantibody; genetics; human leukocyte antigen DRB1; rheumatoid arthritis; systemic lupus erythematosus