Association between vitamin D receptor, CCR5, TNF-α and TNF-β gene polymorphisms and HBV infection and severity of liver disease

Background/Aims: 1,25-dihydroxyvitamin-D is involved in immunomodulation. Expression of vitamin-D receptors in hepatocytes suggests its role in hepatocellular injury. We studied the association of single nucleotide polymorphisms in genes involved in immunoregulatory functions of vitamin-D with susceptibility, severity and persistence of HBV infection. Methods: Five polymorphisms in VDR, CCR5, TNF-alpha and TNF-beta were studied in 214 chronic hepatitis B patients and 408 controls. Clinical parameters were compared between mild or severe liver disease patients. Results: The frequency of heterozygosity of CCR5 Delta 32 was higher in chronic hepatitis B patients than controls (4.2 vs 0.73%, P = 0.005). Frequency of VDR Apa1 a/a and TNF-beta A/A was higher in severe compared with mild liver disease based on HAI (19.3 vs 5.4 %, P = 0.003 and 18.1 vs 3.8%, P = 0.001, respectively) and fibrosis score (23.7 vs 3.6 %, P < 0.001 and 18.1 vs 4.4%, P = 0.002, respectively). The frequency of VDR a/a allele was also higher in patients with higher HBV DNA (11 vs 2.6 %, P = 0.002). Apa1. and TaqI markers in VDR are in linkage-disequilibrium and 'at' haplotype is associated with severe liver disease. Conclusions: CCR5 Delta 32 heterozygosity was associated with susceptibility and VDR a/a, TNF-beta A/A with severity of HBV-related liver disease and VDR a/a allele with higher viral load. These results affirm an important role of immunogenetic factors in the outcome of chronic HBV infection. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.