RRC ID 52508
Author Taipale M, Solovieva S, Leino-Arjas P, Männikkö M.
Title Functional polymorphisms in asporin and CILP together with joint loading predispose to hand osteoarthritis.
Journal BMC Genet
Abstract 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.
Volume 18(1)
Pages 108
Published 2017-12-12
DOI 10.1186/s12863-017-0585-4
PII 10.1186/s12863-017-0585-4
PMID 29233086
PMC PMC5727665
MeSH Aggrecans / metabolism Animals Cells, Cultured Chondrocytes / cytology Chondrocytes / metabolism Cohort Studies Collagen Type II / metabolism Extracellular Matrix Proteins / genetics* Female Genetic Predisposition to Disease* Hand Joints / physiopathology* Humans Mice Middle Aged Occupational Diseases / genetics* Occupational Diseases / pathology Osteoarthritis / genetics* Osteoarthritis / pathology Polymorphism, Genetic Pyrophosphatases / genetics*
IF 2.567
Times Cited 5
Human and Animal Cells ATDC5(RCB0565)