Association study of the functional variants of the GLIS3 gene with risk of knee osteoarthritis.

Abstract

Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population. In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated. We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69-0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61-0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63-0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren-Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46-0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6-0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001). These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together. Key Point • Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.