The causal relationship between antihypertensive drugs and knee osteoarthritis: A drug target Mendelian randomization study

Recently studies have revealed a robust association between hypertension and knee osteoarthritis (KOA), with patients likely to suffer from both conditions. We employed Mendelian randomization (MR) analysis to assess the impact of antihypertensive medications on KOA, aiming to offer clinical guidance for concomitant drug therapy and identify potential therapeutic targets for KOA. We obtained exposure instruments (instrumental variables) by locating Single-nucleotide polymorphisms related to systolic blood pressure near drug target genes. We then conducted Mendelian randomization analyses between the exposure data and genome-wide association studies data on KOA to evaluate the impact of antihypertensive drugs on KOA. We observed a significant association between decreased expression of the SLC12A2 target gene and a reduced risk of KOA (odds ratio: 0.915, 95% confidence interval: 0.869-0.964, P < .001). In this study, we find that SLC12A2 inhibitors can have a beneficial effect on KOA, and that the SLC12A2 gene may be a potential therapeutic target for KOA. These findings suggest that when treating patients with both hypertension and KOA, clinicians may consider prioritizing the use of SLC12A2 inhibitors.