Evaluation of relationship between DNA methyltransferase 3 β gene and the risk of hip osteoarthritis: A case-control...

Osteoarthritis (OA) is a chronic degenerative joint disease. Early studies have indicated that genetic and environmental factors contribute to the risk of OA. However, the etiology of OA remains unknown. Our study aimed to evaluate the association of DNMT3B gene with the risk of hip OA in Han Chinese individuals.

A total of 2070 subjects were recruited into the study, including 658 patients with hip OA and 1412 healthy controls. Twelve tag single nucleotide polymorphisms (SNPs) were selected and genotyped in our samples. Genetic associations between DNMT3B gene and the risk of hip OA were examined at both the single marker and haplotype levels. Cis-expression quantitative trait loci signals that achieve genome-wide significance of targeted SNPs from multiple types of human tissues were extracted from the GTEx database.

Significant signals were identified for SNP rs2424905 in 4 genetic models. The T allele was significantly associated with an increased risk of hip OA (odds ratio = 1.53; 95% CI = 1.28-1.83). The T allele was also significantly associated with higher Kellgren-Lawrence grade in the patients with hip OA (χ²  = 32.70, P = 1.37 × 10^-6 ). Moreover, SNP rs2424905 was significantly associated with the gene expression level of multiple genes, including DNMT3B, C20orf203, COMMD7, EFCAB8, MAPRE1, and RP5-1085F17.3, from several types of human tissues.

Our results indicated that rs2424905 of DNMT3B gene contributed to the risk of hip OA and its clinical severity in a Han Chinese population. These findings suggested that rs2424905 of DNMT3B could be a promising genetic marker to assess susceptibility to hip OA in Han Chinese populations.