title: MICA, a gene contributing strong susceptibility to ankylosing spondylitis.
abstract: OBJECTIVE
  The human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αβ CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS.
  
  
  METHODS
  We examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term.
  
  
  RESULTS
  Sequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS.
  
  
  CONCLUSIONS
  Parallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, The University of Texas Medical School at Houston, Houston, Texas, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hejian
authors.initials: H
authors.lastname: Zou
authors.affiliation: NIAMS, Bethesda, Maryland, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ward
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Weisman
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, The University of Texas Medical School at Houston, Houston, Texas, USA.
authors.forename: Maribel G
authors.initials: MG
authors.lastname: Espitia
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Department of Medicine and Division of Oncology, University of Washington, Seattle, Washington, USA.
authors.forename: Effie
authors.initials: E
authors.lastname: Petersdorf
authors.affiliation: Department of Psychiatry, Stanford University, School of Medicine, Stanford, California, USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
authors.affiliation: The Instituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Armilla, Granada, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.affiliation: Division of Rheumatology, The University of California, San Francisco, USA.
authors.forename: Lianne S
authors.initials: LS
authors.lastname: Gensler
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Scheet
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, The University of Texas Medical School at Houston, Houston, Texas, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Reveille
mesh_terms: D000328:Adult; D001213:Asian / Q000235:genetics* / Q000706:statistics & numerical data; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013167:Spondylitis, Ankylosing / Q000208:ethnology / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data
chemical_list: D005819:Genetic Markers; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A
keywords: Ankylosing Spondylitis; Gene Polymorphism; Inflammation