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.
Suneetha
Pothakamuri Venkata
PV
Department of Gastroenterology, GB Pant Hospital, New Delhi-2, India.
Sarin
Shiv Kumar
SK
Goyal
Ankur
A
Kumar
Gollapudi Tharun
GT
Shukla
Deepak Kumar
DK
Hissar
Syed
S
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