Human beta-Defensins in Primary Sclerosing Cholangitis.

摘要

Objective: Primary Sclerosing Cholangitis (PSC) is a liver disease that is characterized by chronic inflammation of the bile ducts that leads to bile duct injury, cirrhosis and liver failure. Liver transplantation is currently the only long-term treatment of PSC. Therefore, further understanding of PSC and development of treatments are important. Inflammatory diseases have been associated with variations in human β-defensin (HBD) gene copy number. The aim of this study was to investigate whether gene copy number and expression of the gene encoding HBD2 (DEFB4) are associated with PSC.;Methods: The study population consisted of US and Italian cohorts of PSC cases and healthy controls. We estimated HBD gene copy number for PSC patients and healthy controls using both quantitative real-time PCR (qPCR) (US PSC patients n=89, US controls n=87; Italian PSC patients n=46, Italian controls n=84) and paralog ratio test (PRT) (US PSC patients n=83, US controls n=85; Italian PSC patients n=80, Italian controls n=144). Serum levels of HBD2 were measured by ELISA (PSC (N=43), PBC (N=37), or UC (n=42), and healthy controls (N=37).;Results: No significant differences between the frequencies of high DEFB4 gene copy number, defined by greater than 4 copies, and PSC were found in the US, Italian, or combined cohorts. Mean serum levels of HBD2 were significantly greater in PSC (1,086 ± 1,721 ng/µl) compared to PBC (544 ± 754 ng/µl), UC (417 ± 506 ng/µl), and healthy controls (514 ± 731 ng/µl) (p = 0.02).;Conclusions: HBD2 serum levels are increased in PSC but this increase does not appear to be due to differences in copy numbers of its gene.