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J Hepatol. 2006 May;44(5):856-63. Epub 2006 Feb 21.

Association between vitamin D receptor, CCR5, TNF-alpha and TNF-beta gene polymorphisms and HBV infection and severity of liver disease.

Author information

1
Department of Gastroenterology, GB Pant Hospital, New Delhi-2, India.

Abstract

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 CCR5Delta32 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 Taq1 markers in VDR are in linkage-disequilibrium and 'at'haplotype is associated with severe liver disease.

CONCLUSIONS:

CCR5Delta32 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.

PMID:
16545485
DOI:
10.1016/j.jhep.2006.01.028
[Indexed for MEDLINE]

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