Unlike the other class I SLRPs (decorin and biglycan), asporin contains a unique and conserved stretch of aspartate (D) residues in its N terminus, and germline polymorphisms in the D-repeat-length are associated with osteoarthritis and prostate cancer progression.
Asporin is a novel extracellular matrix protein (ECM) with an important role in the development of osteoarthritis (OA), because it has been reported that functional polymorphisms in the aspartic acid repeat (D) of the asporin gene (ASPN) are associated with susceptibility to OA.
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.
Studies examined demonstrate the involvement of asporin in OA pathogenesis, and possible mechanisms by which asporin may be involved in this process have been proposed.
We specifically focused on 3 small leucine-rich repeat proteins (SLRPs), osteomodulin, osteoglycin, and asporin, that appeared to be distinctly regulated in OA labrum compared to OA cartilage.
No association was found between the ASPN D13 and D15 alleles and risk of developing OA by meta-analysis (OR 0.942, 95 % CI 0.840-1.056, p = 0.304; OR 1.050, 95 % CI 0.956-1.154, p = 0.306), respectively.
These findings suggest that polymorphisms within the ASPN gene could influence knee OA susceptibility, but these associations must be confirmed by independent studies in larger samples and different ethnic groups to support the role of the D-repeat polymorphism in the ASPN gene as risk or protection factors for knee OA in a Mexican population.
This finding suggests that ASPN may regulate TGF-beta1-mediated factors in the development of OA, which may provide clues as to the underlying pathology of OA.
Its biological role has been unclear, but recent genetic studies have demonstrated association between asporin and various bone and joint diseases, including osteoarthritis, rheumatoid arthritis and lumbar disc disease.
Our data implied that the -16TT (rs12885713) CALM1 core promoter genotype is not a risk factor for OA etiology in Greek Caucasians on its own, but associated with the Asporin (ASPN) D14 or D15 risk allele, it could influence KOA susceptibility.
Replication studies have confirmed association of functional sequence variations in the secreted frizzled-related protein 3 (FRZB) and asporin (ASPN) genes with osteoarthritis.
Our results indicate that genetic polymorphisms affecting knee OA vary between populations (Japanese versus Caucasian) and sexes and indicate a role for ASPN, COMP, FRZB, and COL2A1 in Caucasians.
It was reported that an aspartic acid (D)-repeat polymorphism in the gene encoding asporin (ASPN) was associated with OA of knee and hip joints in Japanese; in the three independent studies performed, the D14 allele of the ASPN polymorphism was over-represented and the D13 allele was under-represented.