Relationship between the functional exon 3 deleted growth hormone receptor polymorphism and symptomatic osteoarthritis in women
- K M J A Claessen1,
- M Kloppenburg2,
- H M Kroon3,
- J Bijsterbosch2,
- A M Pereira1,
- J A Romijn1,4,
- T van der Straaten5,
- R G H H Nelissen6,
- A Hofman7,
- A G Uitterlinden7,8,9,
- B J Duijnisveld6,
- N Lakenberg10,
- M Beekman9,10,
- J B van Meurs8,9,
- P E Slagboom10,
- N R Biermasz1,
- I Meulenbelt10
- 1Department of Endocrinology and Metabolic Diseases, Center for Endocrine Tumors Leiden, Leiden University Medical Center, Leiden, The Netherlands
- 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
- 3Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
- 4Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
- 5Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
- 6Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands
- 7Department of Epidemiology, Rotterdam, The Netherlands
- 8Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
- 9The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging (NGI-NCHA), Leiden/Rotterdam, The Netherlands
- 10Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
- 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;
- Accepted 12 May 2013
- Published Online First 5 June 2013
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.