To explore whether there are shared genetic risk loci and common disease mechanisms between knee osteoarthritis (KOA) and arteriosclerosis (AS).

Thirty-three subjects enrolled at Peking University Shougang Hospital were divided into a control group (n=8), a KOA group (n=11), and a KOA-AS group (n=14). Candidate single nucleotide polymorphisms (SNPs) were selected through literature review and genome-wide association study (GWAS) data. Genotyping was performed using MassARRAY mass spectrometry, and the results were validated using the FinnGen database. Additionally, targeted metabolomics (UPLC-MS/MS) was employed to detect serum metabolites, analyze their changing trends, and identify enriched pathways.

Among the candidate SNPs tested, the rs1426371 locus (located within the WSCD2 gene) demonstrated a significant difference in allele frequency between the KOA and AS groups, even after Bonferroni correction (P＜0.001). Database validation indicated that this locus is associated with musculoskeletal and metabolic diseases, including type 2 diabetes and hypertension. Metabolomic analysis identified 276 metabolites. Enrichment analysis revealed significant alterations in histidine metabolism and glycine-serine-threonine metabolism pathways in both the KOA and KOA-AS groups, involving metabolites including histamine, imidazoleacetic acid, and glycine.

This preliminary study suggests that rs1426371 may serve as a shared genetic risk locus for KOA and AS. It potentially contributes to the common pathophysiological processes of both diseases by influencing histidine and glycine metabolic pathways. These findings provide genetic and metabolic insights into the "metabolic inflammation" mechanism underlying KOA-AS comorbidity.