Uric acid mediates the association of alpha-1 acid glycoprotein with gallstones in adult women in the United States

Abstract

Gallstones are a common biliary disorder whose pathogenesis may involve alpha-1-acid glycoprotein (AGP), an acute phase inflammatory protein. Serum uric acid (SUA) is the end product of purine metabolism and is associated with a variety of chronic diseases. We conducted a cross-sectional analysis of 1,652 adult women from the 2017-2020 NHANES database to explore the association between AGP levels and gallstone risk and the potential mediating role of SUA. We used multivariate logistic regression, restricted cubic spline curves, subgroup analyses, and causal mediation analyses to evaluate the association between serum AGP levels and gallstone risk.Serum AGP levels were significantly associated with gallstone risk. After correcting for covariates, the highest AGP quartile (≥ 0.950 g/L) was associated with a 1.72-fold higher risk of gallstones compared to the lowest quartile (≤ 0.629 g/L) (OR = 2.72,95% CI: 1.31-5.65; p = 0.014). Subgroup analyses revealed stronger associations in non-Hispanic whites, low-income individuals, and smokers. SUA partially mediated the AGP-gallstone relationship, accounting for 14.76% of the total effect. This study found that AGP levels were significantly associated with gallstone risk in US adult women, and serum uric acid played a mediating role. Future research should further investigate the causal relationship and its applicability in different populations.

Keywords: Alpha-1-acid glycoprotein; Cross-sectional study; Gallstones; Intermediary effect; Uric acid.

Fig. 1

Flowchart for population selection in this study.

Fig. 2

RCS curve fit between AGP and gallstones.Notes: Solid lines represent smooth curve fits between variables.Shaded bands represent 95 per cent confidence intervals from the fit.Subfigure A: no adjustment for covariates. Subfigure B: adjusted for Age、Race、Education level、Family income.Subfigure C: adjusted for Age、Race、Education level、Family income、Current smoking status、Hypertension、Diabetes、C-Reactive Protein、Alanine Aminotransferase (ALT)、Total Calcium、Uric acid、Total Cholesterol.

Fig. 3

Subgroup analysis of the association betweenAGP and gallstones.

Fig. 4

Mediated analysis model path diagram.Notes: AGP was defined as the independent variable; gallstones as the dependent variable; and UA as the mediating variable. Path a represents the regression coefficient of the association between AGP and UA. Path b represents the regression coefficient of the association between UA and gallstones. Path c represents the total effect of AGP on gallstones. Path c’ represents the AGP on gallstones when controlling for UA.

Fig. 5

sensitivity analysis of the mediating effect of uric acid in the relationship between AGP and gallstones. Left: Low-AGP group; Right: High-AGP group. X: Confounding strength (ρ); Y: ACME. Solid = estimate; dashed = 95% CI. Critical ρ: 0.15 Low-AGP) vs. 0.25 (High-AGP).It demonstrates greater robustness to unmeasured confounding in High-AGP individuals compared to Low-AGP individuals.