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BMC Genet. 2017 Dec 12;18(1):108. doi: 10.1186/s12863-017-0585-4.

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

Author information

1
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Aapistie 5, 90220, Oulu, Finland.
2
Biocenter Oulu and Faculty of Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
3
Department of Epidemiology and Biostatistics, Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland.
4
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Aapistie 5, 90220, Oulu, Finland. minna.mannikko@oulu.fi.
5
Biocenter Oulu and Faculty of Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland. minna.mannikko@oulu.fi.

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.

KEYWORDS:

Asporin; Cartilage intermediate layer protein; Functional variant; Genetic association; Osteoarthritis

PMID:
29233086
PMCID:
PMC5727665
DOI:
10.1186/s12863-017-0585-4
[Indexed for MEDLINE]
Free PMC Article

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