Session Title: Osteoarthritis - Clinical Aspects
Session Type: Abstract Submissions (ACR)
Genetic influences contribute considerably to the development of osteoarthritis (OA), and are most likely of a polygenic nature. Until now, genetic studies have identified several genetic variants associated with primary OA, providing strong clue for the involvement of endochondral ossification in OA onset. Endochondral ossification is the main process in longitudinal skeletal growth, and is tightly regulated by a complex network of hormones, growth factors and extracellular matrix components. One of the main players in this process is growth hormone (GH), exerting its effects predominantly through stimulation of insulin-like growth factor-1 (IGF-1) secretion. This qualifies genetic variations within genes involved in the GH/IGF-1 axis as obvious candidates for association studies in primary OA.
Recently, presence of a common growth hormone receptor (GHR) polymorphism, exon 3 deletion (d3-GHR), associated with increased GH sensitivity of the GHR, was demonstrated to have functional consequences in various clinical conditions. The aim of the present study was to investigate the effects of the d3-GHR polymorphism on the extent and characteristics of radiographic in patients with primary OA at multiple joint sites.
In a case-control study, we compared frequency of GHRfl-d3 genotype between patients with familial primary OA from the GARP (Genetics, ARthrosis and Progression) Study, and controls. Kellgren-Lawrence scores were used to assess ROA in the knee, hip and hand; the Osteoarthritis Research Society atlas for the assessment of individual ROA features. Patients and controls were genotyped for 7 single nucleotide polymorphisms (SNPs) encompassing the d3-GHR gene to allow high throughput genotyping. One tagSNP was used as proxy for d3-GHR (full LD, pairwise r2=1). Binary logistic regression analyses with robust standard errors were performed, to assess the relationship between d3-GHR and ROA.
We studied 373 patients (mean age 60.1, 82% female) and 752 controls. GHRfl-d3 genotype was significantly associated with ROA, especially in females (adjusted odds ratio (OR) (95%CI) 1.5(1.1-2.1), p=0.017). Strongest association was found with knee OA (adjusted OR 2.0(1.3-3.0), p=0.002), followed by hand OA (adjusted OR 1.5(1.1-2.1), p=0.024). No such a relationship was found in males. GHRfl-d3 genotype was related to both osteophytes and joint space narrowing.
GHRd3-fl genotype was associated with knee and hand ROA in females with a severe primary OA phenotype, indicating a role for the GH/IGF1 axis in the pathophysiology of primary OA.
K. M. J. A. Claessen,
H. M. Kroon,
A. M. Pereira,
H. A. Romijn,
T. Straaten van der,
P. E. Slagboom,
N. R. Biermasz,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-functional-growth-hormone-receptor-polymorphism-exon-3-deleted-ghr-is-associated-with-radiographic-knee-osteoarthritis-in-females-with-familial-osteoarthritis-at-multiple-sites-the-garp-study/