title: 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 r(2)=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.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Center for Endocrine Tumors Leiden, Leiden University Medical Center, , Leiden, The Netherlands.
authors.forename: K M J A
authors.initials: KM
authors.lastname: Claessen
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
authors.forename: H M
authors.initials: HM
authors.lastname: Kroon
authors.forename: J
authors.initials: J
authors.lastname: Bijsterbosch
authors.forename: A M
authors.initials: AM
authors.lastname: Pereira
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.forename: T
authors.initials: T
authors.lastname: van der Straaten
authors.forename: R G H H
authors.initials: RG
authors.lastname: Nelissen
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: A G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: B J
authors.initials: BJ
authors.lastname: Duijnisveld
authors.forename: N
authors.initials: N
authors.lastname: Lakenberg
authors.forename: M
authors.initials: M
authors.lastname: Beekman
authors.forename: J B
authors.initials: JB
authors.lastname: van Meurs
authors.forename: P E
authors.initials: PE
authors.lastname: Slagboom
authors.forename: N R
authors.initials: NR
authors.lastname: Biermasz
authors.forename: I
authors.initials: I
authors.lastname: Meulenbelt
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics*; D015207:Osteoarthritis, Hip / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011986:Receptors, Somatotropin / Q000235:genetics*; D012737:Sex Factors
chemical_list: D011986:Receptors, Somatotropin
keywords: Chondrocytes; Gene Polymorphism; Osteoarthritis