title: An HLA-C amino-acid variant in addition to HLA-B*27 confers risk for ankylosing spondylitis in the Korean population.
abstract: BACKGROUND
  The presence of the HLA-B*27 allele is a major risk factor for the development of ankylosing spondylitis (AS), which causes chronic inflammation of the spine and other sites. We investigated residual effects outside HLA-B within the major histocompatibility complex (MHC) region in the Korean population.
  
  
  METHODS
  Using the Korean HLA reference panel, we inferred the classic HLA alleles and amino-acid residues of the six HLA genes (HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1) and MHC single-nucleotide polymorphisms in 3820 Korean subjects, including 654 Korean cases of AS and 3166 controls, who were genotyped by using Immunochip. Logistic regression and log-likelihood ratio tests were used in AS association tests for imputed markers.
  
  
  RESULTS
  The most significant associations were identified at amino-acid positions in the epitope-binding site of HLA-B (P = 1.71 × 10(-481) at position 70, P = 7.20 × 10(-479) at position 97, and P = 2.54 × 10(-484) at positions 114), highlighting the risk effect of the HLA-B*27 allele and the protective effects of other classic alleles. A secondary effect was located at the leucine at amino-acid position 116 in the epitope-binding site of HLA-C (P = 1.69 × 10(-14)), completely tagging the HLA-C*15:02 allele. This residue had a large effect in HLA-B*27-negative patients (odds ratio = 6.6, 95 % confidence interval = 3.8 to 11.4).
  
  
  CONCLUSIONS
  The four amino-acid positions of HLA-B and -C account for most of the associations between AS and MHC in the Korean population. This finding updates the list of AS susceptibility loci and provides new insight into AS pathogenesis mediated by MHC class I molecules.
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. atgc@hanyang.ac.kr.
authors.forename: Kwangwoo
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. sybang@hanyang.ac.kr.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Bang
authors.affiliation: Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. radsh@hanyang.ac.kr.
authors.forename: Seunghun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. lhsberon@hanyang.ac.kr.
authors.forename: Hye-Soon
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University Hospital, 282, Munhwa-ro, Jung-gu, Daejeon, 35015, Republic of Korea. shimsc@cnuh.co.kr.
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Shim
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kyungpook National University School of Medicine, 680, Gukchaebosang-ro, Jung-gu, Daegu, 41944, Republic of Korea. ymkang@knu.ac.kr.
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.affiliation: Department of Rheumatology, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea. chsuh@ajou.ac.kr.
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Suh
authors.affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK, 73104, USA. celi-sun@omrf.org.
authors.forename: Celi
authors.initials: C
authors.lastname: Sun
authors.affiliation: Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK, 73104, USA. swapan-nath@omrf.org.
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Nath
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. scbae@hanyang.ac.kr.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. thkim@hanyang.ac.kr.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
mesh_terms: D044466:Asian People / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000235:genetics*
chemical_list: D015235:HLA-B Antigens; D015236:HLA-C Antigens