title: Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment.
abstract: OBJECTIVE
  To determine the relative effects of genetic and environmental factors in susceptibility to ankylosing spondylitis (AS).
  
  
  METHODS
  Twins with AS were identified from the Royal National Hospital for Rheumatic Diseases database. Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed using a combination of validated scoring systems. HLA typing for HLA-B27, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction with sequence-specific primers, and zygosity was assessed using microsatellite markers. Genetic and environmental variance components were assessed with the program Mx, using data from this and previous studies of twins with AS.
  
  
  RESULTS
  Six of 8 monozygotic (MZ) twin pairs were disease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twin pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignificant increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concordant MZ twins compared with concordant DZ twins. HLA-B27 and B60 were associated with the disease in probands, and the rate of disease concordance was significantly increased among DZ twin pairs in which the co-twin was positive for both B27 and DR1. Additive genetic effects were estimated to contribute 97% of the population variance.
  
  
  CONCLUSIONS
  Susceptibility to AS is largely genetically determined, and the environmental trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Headington, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Brown
authors.forename: L G
authors.initials: LG
authors.lastname: Kennedy
authors.forename: A J
authors.initials: AJ
authors.lastname: MacGregor
authors.forename: C
authors.initials: C
authors.lastname: Darke
authors.forename: E
authors.initials: E
authors.lastname: Duncan
authors.forename: J L
authors.initials: JL
authors.lastname: Shatford
authors.forename: A
authors.initials: A
authors.lastname: Taylor
authors.forename: A
authors.initials: A
authors.lastname: Calin
authors.forename: P
authors.initials: P
authors.lastname: Wordsworth
mesh_terms: D000328:Adult; D000368:Aged; D004198:Disease Susceptibility / Q000276:immunology; D004200:Diseases in Twins / Q000235:genetics*; D004777:Environment; D006680:HLA Antigens / Q000502:physiology*; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D006680:HLA Antigens; D015796:HLA-B27 Antigen