Abstract
BackgroundOsteoarthritis (OA) is the most common degenerative joint disease afflicting people in the Western world and has a strong genetic influence. The aim of this study was to examine the association of two known functional polymorphisms in the TGF-β inhibiting genes, asporin (ASPN) and cartilage intermediate layer protein (CILP), with hand OA and potential gene-occupational hand loading interaction.ResultsStatistically significant interaction of the CILP rs2073711 T and ASPN D15 alleles with hand OA was observed (OR = 2.48, 95% CI 1.27–4.85, p = 0.008) in a Finnish hand OA cohort of 543 women (aged 45–63). When stratified by variation in working tasks, low variation of working tasks increased the risk further (OR = 3.00, 95% CI 1.35–6.66, p = 0.007). Based on the analysis of ASPN and CILP protein-coding regions, functional studies were performed with one observed variant, rs41278695 in the ASPN gene. Analyses showed that bone morphogenetic protein 2 (BMP2) mediated expression of aggrecan (Agc1) and type II collagen (Col2a1) was significantly suppressed (p = 0.011 and p = 0.023, respectively) in a murine chondrocytic cell line (ATDC5) with cells stably expressing ASPN rs41278695.ConclusionsThe carriage of either ASPN D15 or CILP rs2073711 TT is associated with increased risk of symmetrical hand OA, particularly in individuals with low variation in work tasks. ASPN rs41278695 SNP had an effect on Agc1 and Col2a1 gene expression when induced with BMP-2 suggesting an effect on the cartilage extracellular matrix composition.
Highlights
Osteoarthritis (OA) is the most common degenerative joint disease afflicting people in the Western world and has a strong genetic influence
The carriage of either ASPN D15 or cartilage intermediate layer protein (CILP) rs2073711 TT is associated with increased risk of symmetrical hand OA, in individuals with low variation in work tasks
ASPN rs41278695 single nucleotide polymorphism (SNP) had an effect on Agc1 and Col2a1 gene expression when induced with Bone morphogenetic protein (BMP)-2 suggesting an effect on the cartilage extracellular matrix composition
Summary
Osteoarthritis (OA) is the most common degenerative joint disease afflicting people in the Western world and has a strong genetic influence. The aim of this study was to examine the association of two known functional polymorphisms in the TGF-β inhibiting genes, asporin (ASPN) and cartilage intermediate layer protein (CILP), with hand OA and potential gene-occupational hand loading interaction. Osteoarthritis (OA) is a joint disorder involving degeneration of the cartilage, and affecting surrounding tissues [1]. OA disables often weight-bearing joints such as hip and knee, but the most frequent site is in the hand, among women over 50 years of age [2]. Between 39% to 65% of the hand and knee OA in women are associated with genetic factors [3]. Overloading as well as reduced loading increases cartilage matrix degeneration [6, 7]
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