Investigation of NPC1L1 and NPC2 Protein Levels in Patients with Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation

Cholelithiasis is a common hepatobiliary disorder associated with impaired cholesterol homeostasis and chronic inflammation. Niemann–Pick C1-Like 1 (NPC1L1) and Niemann–Pick C2 (NPC2) are proteins involved in cholesterol transport; however, their roles in the pathogenesis of cholelithiasis remain unclear. This case–control study investigated serum NPC1L1 and NPC2 levels in 44 patients with cholelithiasis and 44 healthy controls. Serum concentrations of NPC1L1 and NPC2 were measured using enzyme-linked immunosorbent assay (ELISA). Group comparisons, receiver operating characteristic (ROC) curve analysis, Spearman correlation analysis, and multivariable logistic regression were performed. Patients with cholelithiasis were significantly older than controls (p<0.001). Serum NPC1L1 levels showed a decreasing trend in patients but did not differ significantly between groups (p=0.060), whereas serum NPC2 levels were significantly higher in patients with cholelithiasis (p=0.019). ROC analysis demonstrated diagnostic performance for NPC2 (area under the curve [AUC] = 0.640, p=0.019), while NPC1L1 did not reach statistical significance (AUC=0.616, p=0.060). A weak negative correlation was observed between NPC1L1 and NPC2 levels (r=−0.221, p=0.038). Multivariable logistic regression analysis indicated that neither NPC1L1 nor NPC2 was independently associated with cholelithiasis, whereas age remained independently associated with cholelithiasis in the adjusted models. These findings suggest that altered NPC1L1 and NPC2 levels may be associated with cholelithiasis. However, the modest discriminatory performance of NPC2 indicates that these findings should be considered exploratory and require validation in larger studies.