Association of SPP1 promoter variants with hip osteoarthritis susceptibility in Chinese population

• Association of SPP1 variants with hip osteoarthritis was studied.
• rs17524488 in SPP1 gene confers high risk for hip osteoarthritis.
• rs17524488 affects SPP1 expression in hip tissues.

Three genetic variants in the promoter of SPP1 (secreted phosphoprotein 1) gene have been reported to affect transcriptional activity of SPP1, thus conferring an increased risk for some diseases. To testify if these variants are associated with risk of hip osteoarthritis (OA) as well, we performed a case–control study including 389 hip OA patients and 315 healthy controls. Genotypes of SPP1 were determined by DNA sequencing, and differential expressions of SPP1 in relation with genotypes were evaluated by RT-PCR and ELISA. The results showed that rs17524488 (delG > insG) increased the risk of hip OA, with the adjusted OR 1.48 (95% CI 1.18–1.85, P < 0.01) for risk allele insG, 1.90 (95% CI 1.35–2.66, P < 0.01) for delG/insG and 2.04 (95% CI 1.20–3.49, P < 0.01) for insG/insG respectively. However, as for rs11730582 (T > C), the adjusted ORs were 1.18 (95% CI 0.94–1.49, P = 0.148) for allele C, 1.26 (95% CI 0.90–1.75, P = 0.158) for TC, and 1.31 (95% CI 0.77–2.24, P = 0.293) for CC, indicating no association of rs11730582 with hip OA risk. The variant rs28357094 was not observed in the tested subjects. Furthermore, the delG/insG and insG/insG genotypes of rs17524488 both correlated with higher levels of SPP1 expression in articular cartilage (P < 0.01 for all comparisons) as well as in in synovial fluid (P < 0.01 for all comparisons) compared with delG/delG, while rs11730582 had no effect on the SPP1 expression (P > 0.05 for all comparisons). These results collectively indicate that the genetic variant rs17524488 in SPP1 promoter confers high risk for hip OA in a Chinese population, possibly through enhancing SPP1 expression.