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ANKH variants associated with ankylosing spondylitis: gender differences.

Hing Wo Tsui1, Robert D Inman, Andrew D Paterson

  • 1Toronto Western Research Institute, Toronto, Ontario, Canada. htsui@uhnres.utoronto.ca

Arthritis Research & Therapy
|May 19, 2005
PubMed
Summary

Genetic variants in the ANKH gene are associated with ankylosing spondylitis (AS). Specific ANKH gene regions show gender-specific associations, suggesting a role in AS susceptibility.

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Area of Science:

  • Genetics
  • Immunology
  • Rheumatology

Background:

  • Ankylosing spondylitis (AS) is an inflammatory disease with a strong genetic component.
  • The progressive ankylosis (ank) mouse model shares similarities with human AS.
  • Previous studies identified modest associations between ANKH gene markers and AS.

Purpose of the Study:

  • To extensively evaluate ANKH gene variants associated with AS.
  • To determine if ANKH variant associations with AS are gender-specific.

Main Methods:

  • Family-based association analyses were conducted on 201 multiplex AS families.
  • Nine intragenetic and two flanking microsatellite markers within the ANKH gene were genotyped.
  • Haplotype analyses and tests of interaction were performed to assess gender-specific associations.

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Main Results:

  • ANKH gene variants in two distinct regions were associated with AS.
  • A specific haplotype (rs26307[C] and rs27356[C]) was significantly associated with AS in men.
  • Another haplotype (rs28006[C] and rs25957[C]) was significantly associated with AS in women.
  • rs26307 showed a gender-specific difference in association strength.
  • The region associated with AS in women demonstrated significance in interaction tests within families of both genders.

Conclusions:

  • ANKH gene variants play a role in genetic susceptibility to ankylosing spondylitis.
  • A significant gender-genotype specificity exists in the association between ANKH variants and AS.