BackgroundThe association between serum uric acid (SUA) levels and serum PCSK9 levels has not yet been uncovered. This study aimed to explore the potential link between SUA levels and serum PCSK9 levels and quantify the mediating effect of metabolic factors and inflammation in Chinese adults. Furthermore, assessed whether gender differences modified this association. MethodsIn total, 2624 participants were enrolled and categorized based on their serum UA levels as the hypouricemic (n=432) and normouricemic group (n=2192). Stepwise multivariable regression analysis, binary logistic regression analysis and mediation analyses were performed. ResultsParticipants with hyperuricemia had higher serum PCSK9 levels than those with normouricemia (73.74±30.25 vs 68.55±29.01ng/ml, P<0.05), especially in women (69.11±28.84 vs 87.86±27.90ng/ml, P<0.001). SUA levels were positively associated with serum PCSK9 levels in all participants (r=0.06, P<0.01) and in women (r=0.22, P<0.01), but not in men (r=0.03, P=0.18). Multiple linear regression and binary logistic regression analyses indicated that serum PCSK9 levels were significantly correlated with SUA levels and hyperuricemia in women. However, when the model was adjusted for triglyceride (TG), the associations of serum PCSK9 levels with SUA levels and hyperuricemia disappeared. In mediation analyses, TG, low-density lipoprotein cholesterol (LDL-C), body mass index(BMI), total cholesterol (TC), white blood cell count and neutrophil count explained 35.08%, 20.58%,19.99%, 14.37%, 7.10% and 3.24% of SUA levels association with serum PCSK9 levels, respectively. ConclusionSerum PCSK9 levels are positively associated with SUA levels in women. Furthermore, this association is partially mediated through metabolic factors and inflammation.