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Clinical and epidemiological research
Concise report
Relationship between the functional exon 3 deleted growth hormone receptor polymorphism and symptomatic osteoarthritis in women
  1. K M J A Claessen1,
  2. M Kloppenburg2,
  3. H M Kroon3,
  4. J Bijsterbosch2,
  5. A M Pereira1,
  6. J A Romijn1,4,
  7. T van der Straaten5,
  8. R G H H Nelissen6,
  9. A Hofman7,
  10. A G Uitterlinden7,8,9,
  11. B J Duijnisveld6,
  12. N Lakenberg10,
  13. M Beekman9,10,
  14. J B van Meurs8,9,
  15. P E Slagboom10,
  16. N R Biermasz1,
  17. I Meulenbelt10
  1. 1Department of Endocrinology and Metabolic Diseases, Center for Endocrine Tumors Leiden, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
  4. 4Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
  5. 5Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
  6. 6Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands
  7. 7Department of Epidemiology, Rotterdam, The Netherlands
  8. 8Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
  9. 9The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/Rotterdam, The Netherlands
  10. 10Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Kim M J A Claessen, Department of Endocrinology and Metabolic Diseases C7-Q, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands; K.M.J.A.Claessen{at}lumc.nl

Abstract

Background Several studies suggest a role of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in the pathophysiology of primary osteoarthritis (OA). A common polymorphism of the GH receptor (exon 3 deletion, d3-GHR) is associated with increased GH/IGF-1 activity.

Objective To study associations between the d3-GHR polymorphism and symptomatic OA.

Methods In the GARP (Genetics, osteoARthritis and Progression) study, we compared the d3-GHR polymorphism between OA patients and controls. GARP patients were genotyped for seven single nucleotide polymorphisms encompassing the d3-GHR gene, using rs4590183 as proxy for d3-GHR (pairwise r2=1). Binary logistic regression models with robust SEs were performed, stratified by sex. For replication, rs4590183 was tested in three additional cohorts. Fixed- and random-effects combined analyses were performed.

Results In female GARP patients with severe familial OA, d3-GHR was associated with OA (adjusted OR 1.36 (95% CI 1.01 to 1.83), p=0.043), independently of age and body mass index. Combined analysis of all studies showed suggestive evidence for association between d3-GHR and OA (OR=1.17 (95% CI 1.04 to 1.30), p=0.008). Evidence was strongest in hip OA cases, without any evidence for heterogeneity.

Conclusions In women, the d3-GHR polymorphism was associated with symptomatic OA, especially at the hip site.

  • Osteoarthritis
  • Gene Polymorphism
  • Chondrocytes

https://doi.org/10.1136/annrheumdis-2012-202713

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