TY - JOUR
T1 - Relationship between the functional exon 3 deleted growth hormone receptor polymorphism and symptomatic osteoarthritis in women
AU - Claessen, K. M. J. A.
AU - Kloppenburg, M.
AU - Kroon, H. M.
AU - Bijsterbosch, J.
AU - Pereira, A. M.
AU - Romijn, J. A.
AU - van der Straaten, T.
AU - Nelissen, R. G. H. H.
AU - Hofman, A.
AU - Uitterlinden, A. G.
AU - Duijnisveld, B. J.
AU - Lakenberg, N.
AU - Beekman, M.
AU - van Meurs, J. B.
AU - Slagboom, P. E.
AU - Biermasz, N. R.
AU - Meulenbelt, I.
PY - 2014
Y1 - 2014
N2 - 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
AB - 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
U2 - https://doi.org/10.1136/annrheumdis-2012-202713
DO - https://doi.org/10.1136/annrheumdis-2012-202713
M3 - Article
C2 - 23740230
SN - 0003-4967
VL - 73
SP - 433
EP - 436
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 2
ER -