Research Article

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

Volume: 47 Number: 5 October 27, 2026

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

Abstract

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.

Keywords

Biomarker, Cholelithiasis, Cholesterol transport, NPC1L1, NPC2

Ethical Statement

Approval No. 2025-05/10

References

  1. Di Ciaula, A., Wang, D. Q., & Portincasa, P. (2018). An update on the pathogenesis of cholesterol gallstone disease. Current Opinion in Gastroenterology, 34(2), 71–80. https://doi.org/10.1097/MOG.0000000000000423
  2. Costa, C. J., Nguyen, M. T. T., Vaziri, H., & Wu, G. Y. (2024). Genetics of gallstone disease and their clinical significance: A narrative review. Journal of Clinical and Translational Hepatology, 12(3), 316–333. https://doi.org/10.14218/JCTH.2023.00563
  3. Li, X., Zhang, Y., Liu, H., Wang, J., & Chen, L. (2025). Relationship between abnormal lipid metabolism and gallstone formation. Lipids in Health and Disease, 85(1), 11–21. https://doi.org/10.4166/kjg.2024.135
  4. Zheng, L., Ye, Z. Y., & Ma, J. J. (2025). Effect of cholesterol metabolism on hepatolithiasis. World Journal of Gastroenterology, 31(1), 99960. https://doi.org/10.3748/wjg.v31.i1.99960
  5. Hasyyati, E. Y., Prasetyo, B., Rahman, A., Putri, D. A., & Nurhayati, S. (2026). In silico investigation of DLBS3233 bioactives targeting inflammatory, metabolic, and cholesterol transport pathways in gallstone (cholelithiasis) pathogenesis. Journal of Molecular Modeling, 46(1). https://doi.org/10.12873/461baulia
  6. Xiao, J., Zhang, Y., Li, Y., Wang, Z., Chen, X., & Xu, G. (2023). Bile acids-mediated intracellular cholesterol transport promotes intestinal cholesterol absorption and NPC1L1 recycling. Nature Communications, 14(1), 6469. https://doi.org/10.1038/s41467-023-42179-5
  7. Mo, P., Chen, H., Xu, G., Li, Y., & Wang, J. (2023). Effect of hepatic NPC1L1 on cholesterol gallstone disease and its mechanism. JHEP Reports, 9(5). https://doi.org/10.1016/j.heliyon.2023.e15757
  8. Chen, H., Mo, P., & Xu, G. (2025). Potential function of hepatic Niemann–Pick C1-like 1: Cholesterol homeostasis regulation of the canalicular lipid bilayer membrane. Glycative Research, 13, goaf010. https://doi.org/10.1093/gastro/goaf010
  9. Javanshad, R., Smith, A., Brown, T., & Jones, P. (2025). Advances in mass spectrometry of lipids for the investigation of Niemann–Pick type C disease. Mass Spectrometry Reviews, 24(1), 254. https://doi.org/10.1186/s12944-025-02675-7
  10. Zhang, C., Liu, H., Wang, L., Zhao, X., & Chen, J. (2024). Advances in research on potential therapeutic approaches for Niemann–Pick C1 disease. Frontiers in Cell and Developmental Biology, 15, 1465872. https://doi.org/10.3389/fphar.2024.1465872
APA
Genç, H. Ç., Coşkun, H., Zontul, C., Taş, A., Topcu, Ö., & Siliğ, Y. (2026). Investigation of NPC1L1 and NPC2 Protein Levels in Patients with Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation. Cumhuriyet Science Journal, 47(5), 791-799. https://doi.org/10.17776/csj.1981819
AMA
1.Genç HÇ, Coşkun H, Zontul C, Taş A, Topcu Ö, Siliğ Y. Investigation of NPC1L1 and NPC2 Protein Levels in Patients with Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation. CSJ. 2026;47(5):791-799. doi:10.17776/csj.1981819
Chicago
Genç, Hüsnü Çağrı, Hakkı Coşkun, Cemile Zontul, Ayça Taş, Ömer Topcu, and Yavuz Siliğ. 2026. “Investigation of NPC1L1 and NPC2 Protein Levels in Patients With Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation”. Cumhuriyet Science Journal 47 (5): 791-99. https://doi.org/10.17776/csj.1981819.
EndNote
Genç HÇ, Coşkun H, Zontul C, Taş A, Topcu Ö, Siliğ Y (October 1, 2026) Investigation of NPC1L1 and NPC2 Protein Levels in Patients with Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation. Cumhuriyet Science Journal 47 5 791–799.
IEEE
[1]H. Ç. Genç, H. Coşkun, C. Zontul, A. Taş, Ö. Topcu, and Y. Siliğ, “Investigation of NPC1L1 and NPC2 Protein Levels in Patients with Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation”, CSJ, vol. 47, no. 5, pp. 791–799, Oct. 2026, doi: 10.17776/csj.1981819.
ISNAD
Genç, Hüsnü Çağrı - Coşkun, Hakkı - Zontul, Cemile - Taş, Ayça - Topcu, Ömer - Siliğ, Yavuz. “Investigation of NPC1L1 and NPC2 Protein Levels in Patients With Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation”. Cumhuriyet Science Journal 47/5 (October 1, 2026): 791-799. https://doi.org/10.17776/csj.1981819.
JAMA
1.Genç HÇ, Coşkun H, Zontul C, Taş A, Topcu Ö, Siliğ Y. Investigation of NPC1L1 and NPC2 Protein Levels in Patients with Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation. CSJ. 2026;47:791–799.
MLA
Genç, Hüsnü Çağrı, et al. “Investigation of NPC1L1 and NPC2 Protein Levels in Patients With Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation”. Cumhuriyet Science Journal, vol. 47, no. 5, Oct. 2026, pp. 791-9, doi:10.17776/csj.1981819.
Vancouver
1.Hüsnü Çağrı Genç, Hakkı Coşkun, Cemile Zontul, Ayça Taş, Ömer Topcu, Yavuz Siliğ. Investigation of NPC1L1 and NPC2 Protein Levels in Patients with Cholelithiasis: Implications for Cholesterol Transport and Gallbladder Inflammation. CSJ. 2026 Oct. 1;47(5):791-9. doi:10.17776/csj.1981819