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Relationship between the functional exon 3 deleted growth hormone receptor polymorphism and symptomatic osteoarthritis in women

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

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