Variation at the ANP32A gene is associated with risk of hip osteoarthritis in women

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Ana M Valdes1, Rik J Lories, Joyce B van Meurs

  • 1Kings College London, London, UK. ana.valdes@kcl.ac.uk

Arthritis and Rheumatism
|July 1, 2009
PubMed
Abstract

Insights

Genetic variations in the ANP32A gene are linked to a reduced risk of osteoarthritis (OA), particularly hip OA. This suggests ANP32A plays a role in OA development.

Area of Science:

  • Genetics and Molecular Biology
  • Rheumatology
  • Osteoarthritis Research

Background:

  • The ANP32A gene encodes a tumor suppressor involved in apoptosis and Wnt signaling.
  • Osteoarthritis (OA) is a prevalent degenerative joint disease with complex genetic underpinnings.

Purpose of the Study:

  • To investigate the association between genetic variations in the ANP32A gene and the risk of developing osteoarthritis (OA) in women.
  • To determine if specific single-nucleotide polymorphisms (SNPs) in ANP32A correlate with hip or knee OA.

Main Methods:

  • Genotyping of ANP32A SNPs in a large case-control study including women with total knee replacements (TKRs) and total hip replacements (THRs).
  • Validation of associated SNPs in independent cohorts (Chingford, Rotterdam, and TwinsUK Studies) with clinical and radiographic OA data.
  • Meta-analysis of hip OA data across multiple cohorts to assess the overall association.

Main Results:

  • ANP32A transcript expression was high in normal and OA articular cartilage.
  • Three ANP32A SNPs showed significant association with hip OA in the Nottingham cohort.
  • The minor allele of rs7164503 was significantly associated with a reduced risk of hip OA (OR 0.67, P < 3.8 x 10(-4)) and showed a trend for knee OA.

Conclusions:

  • The study provides evidence for ANP32A's involvement in the pathogenesis of hip osteoarthritis.
  • Genetic variations in ANP32A may influence susceptibility to OA, particularly of the hip.

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