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Background  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  .Results  Statistically 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.    Conclusions  The 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.

Functional polymorphisms in asporin and CILP together with joint loading predispose to hand osteoarthritis