Genetic polymorphisms of SPP1 and MGP are associated with thumb osteoarthritis: a replication study in the Chinese population.

BACKGROUND

In a recent meta-analysis of genome-wide association studies, three novel common variants were reported to be associated with erosive hand osteoarthritis. In this study, we aimed to investigate whether rs17013495, rs11243284 and rs1800801 are associated with the development of thumb OA in the Chinese population.

METHODS

All three were genotyped in 529 patients and 822 healthy controls. The gene expression was evaluated in synovium tissue samples collected from 32 patients undergoing trapeziectomy. The Chi-square analysis was performed to compare the frequency of allele frequency between the patients and controls. The Kruskal-Wallis test was used to compare the mRNA expression between patients with different genotypes.

RESULTS

For rs17013495, the frequency of allele T in the patients was significantly higher than that in the controls (0.649 vs. 0.582, p = 0.001). For rs1800801, the frequency of allele T in the patients was significantly higher than that in the controls (0.156 vs. 0.117, p = 0.004) The mRNA expression of SPP1 was 1.46 folds higher in patients with genotype TC/CC than in the patients with genotype TT (p = 0.02). The mRNA expression of MGP was 1.72 folds higher in patients with genotype CC than in the patients with genotype TT/TC (p = 0.03).

CONCLUSIONS

Variant rs1800801 of MGP and rs17013495 of SPP1 were associated with the susceptibility of thumb OA in the Chinese population. For both variants, allele T can add to the risk of thumb OA possibly via down-regulation of MGP and SPP1 expression.