Genomic Medicine

Osteoarthritis (OA) is a chronic joint disease with genetic as well as environmental factors contributing to its etiology. We recently identified RHOB as a gene overexpressed in osteoarthritis. Interestingly, RHOB harbors numerous polymorphisms in its promoter region and genotyping of OA patients and healthy controls revealed an association of the single nucleotide polymorphism (SNP) rs585017 with the disease. We here set out to investigate the influence of RHOB promoter polymorphisms on the transcriptional activity of the gene and we found evidence that the SNPs rs2602160 and rs585017 cooperate in regulating RHOB expression. In addition, a variable number of tandem repeats (VNTR) impacts on the RHOB transcriptional activity in a cell type restricted manner. These results mechanistically link our previous finding of an elevated RHOB expression to the disease associated SNP rs585017 and confirm a role for regulatory polymorphisms in osteoarthritis.