Association between vitamin D receptor, CCR5, TNF-alpha and TNF-beta gene polymorphisms and HBV infection and severity of liver disease.
OBJECTIVE
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.
Department of Gastroenterology, GB Pant Hospital, New Delhi-2, India.
Pothakamuri Venkata
PV
Suneetha
Shiv Kumar
SK
Sarin
Ankur
A
Goyal
Gollapudi Tharun
GT
Kumar
Deepak Kumar
DK
Shukla
Syed
S
Hissar
D000328:Adult; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019713:Receptors, CCR5 / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D019562:Viral Load
D005819:Genetic Markers; D008233:Lymphotoxin-alpha; D019713:Receptors, CCR5; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha