Aim: Previous studies have provided evidence linking the DPEP1 gene to the risk of osteoarthritis (OA) in Europeans. In this study, we aimed to examine the relationship between DPEP1 gene and the susceptibility and clinical severity of OA in a Chinese Han population.
Methods: This study comprised two independent samples. For the discovery stage, 1022 patients with knee OA and 1864 controls were recruited. Fourteen tag single nucleotide polymorphisms (SNPs) covering the DPEP1 gene were selected and genotyped. Associated SNPs in the discovery data set were subsequently genotyped in the replication data set consisting of 826 hip OA cases and 1662 controls. Both genotypic and allelic genetic associations were tested. The relationship of significant SNPs to the expression of DPEP1 and its neighboring genes was examined using the GTEx database.
Results: A nonsynonymous SNP, rs1126464, was determined to be associated with the disease status of OA in both the discovery and replication stages (odds ratio [OR] 0.75, 95% confidence interval [95% CI] 0.68-0.82, P = 7.16 × 10-11 ). This SNP was further characterized as being significantly related to a higher Kellgren-Lawrence grade in OA patients (OR 0.64, 95% CI 0.55-0.74, P = 2.53 × 10-9 ). According to the GTEx data, SNP rs1126464 was significantly related to the gene expression of 15 genes in multiple types of human tissues.
Conclusion: We reported a common DNA variant in the DPEP1 gene that contributes to the risk of OA, providing additional evidence that the DPEP1 gene plays a significant role in the pathological mechanisms of OA.
Keywords: DPEP1 gene; case-control study; osteoarthritis; single nucleotide polymorphism.
© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.