Association of lipids and lipid-lowering drug target genes with Osteomyelitis : A mendelian randomization analysis

Abstract Background: Studies have shown that lipid metabolism is a key regulator of inflammation in acute and chronic conditions. However, it is currently unclear whether dyslipidemia is related to the process of osteomyelitis. To explore the link between lipid characteristics and osteomyelitis, our study used MR analysis to explore the link between triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and osteomyelitis. Besides, the link between the gene targets corresponding to these traits and osteomyelitis was further explored. Method: Genetic variants associated with TG and TC are selected from the Global Lipids Genetics Consortium, while LDL-C datasets were extracted from UK Biobank. Osteomyelitis was identified in FinnGen consortium (R10). The lipid-lowering drug targets showing significance were additionally assessed using the inflammatory response marker C-reactive protein (CRP). Furthermore, mediation analyses were performed to validate the reliability of the findings and explore potential mediating factors. Result: No association was found between LDL-C, TG, or TC and osteomyelitis. Proprotein convertase subtilisin/kexin type 9(PCSK9) was significantly associated with lower osteomyelitis risk in the dataset(OR [95%Cl] = 0.49[0.32 to 0.76], p = 1.60×10 − 3). PCSK9 was significantly associated with lower CRP risk(OR [95%Cl] = 0.94[0.92 to 0.97], p = 3.16×10 − 4). Our results support waist circumference as an intermediate variable between PCSK9 and osteomyelitis. Conclusion: This study does not support the relationship between dyslipidemia and osteomyelitis. PCSK9 was found to be significantly associated with a lower risk of osteomyelitis. Our study supports that waist circumference may be a potential mediator between osteomyelitis and PCSK9. In addition, we found that PCSK9 showed a reduction in CRP levels.