Abstract
Several polymorphisms in the vitamin D receptor (VDR) are associated with the occurrence of chronic liver disease. Here, we investigated the association between BsmI, ApaI, TaqI and FokI VDR polymorphisms and the severity of liver cirrhosis in relation to serum cytokine and lipopolysaccharide binding protein (LBP) levels and their role on survival in cirrhotic patients. We found that patients harboring the BB genotype had higher MELD score, and they were mainly at CP stage C; patients harboring the AA genotype had increased LBP, IL-1β and IL-8 levels, and they were mostly at CP stage C; TT genotype carriers had higher MELD score and they were mainly at CP stage C and FF genotype carriers had lower IL-1β levels when compared to Bb/bb, Aa/aa, Tt/tt and Ff/ff genotypes respectively. In the multivariate analysis ApaI, BsmI and TaqI polymorphisms were independently associated with liver cirrhosis severity. In the survival analysis, the independent prognostic factors were CP score, MELD and the FF genotype. Our results indicate that the ApaI, TaqI and BsmI polymorphisms are associated with the severity of liver cirrhosis, through the immunoregulatory process. Survival is related to the FF genotype of FokI polymorphism, imparting a possible protective role in liver cirrhosis.
Highlights
Liver cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, and is associated with the development of liver failure and portal hypertension[1,2]
Recent studies have shown that there is a genetic association of vitamin D receptor (VDR) polymorphisms to autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), HBV infection and hepatocellular carcinoma (HCC)[8,10,11,12,13,14,15,16,17]
We have investigated the potential associations between VDR gene polymorphisms and the severity of liver cirrhosis, in relation to the cytokine and bacterial profiles, vitamin D and vitamin D binding protein (VDBP) levels, and their role on patient survival
Summary
Liver cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, and is associated with the development of liver failure and portal hypertension[1,2]. The ApaI and the BsmI polymorphisms are located in intron 8 at the 3′ end of the VDR gene. These polymorphisms do not change the amino acid sequence of the VDR protein. BsmI and ApaI may affect gene expression through the alteration of mRNA stability, the disruption of splice sites for mRNA transcription, or a change in intronic regulatory elements[8,9]. Recent studies have shown that there is a genetic association of VDR polymorphisms to autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), HBV infection and hepatocellular carcinoma (HCC)[8,10,11,12,13,14,15,16,17]. P-value p-value existence of VDR polymorphisms in patients with PBC10 and HCV18 and with reduced full-length VDR protein expression, but increased VDR protein fragments in patients with NAFLD10,18,19
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
