Interleukin-1, interleukin-10 and tumour necrosis factor-alpha gene polymorphisms in hepatitis C virus infection: an investigation of the relationships with spontaneous viral clearance and response to alpha-interferon therapy.
OBJECTIVE
Though there is a consensus that the HLA DQB1*0301 allele is important in untreated HCV clearance, this association is not universal and a number of genes outside the major histocompatibility complex may also play a role in host responses to HCV infection. Prime candidates, at present, are the genes encoding pro-inflammatory and immuno-regulatory cytokines. The aim of this study was to investigate the relationship between a number of these candidate genes and both spontaneous and treatment related clearance of hepatitis C virus infection.


METHODS
Three members of the interleukin-1 gene family: IL-1A, IL-1B and IL-1RN, three polymorphic sites in the interleukin-10 gene promoter (- 1082, - 819, - 592) and two in the tumour necrosis factor-alpha promoter (- 308, - 238) were studied in two independent DNA banks, each with appropriate controls. Standard PCR-based genotyping techniques were used.


RESULTS
No significant difference in the distribution of any of the polymorphisms was found in either study set.


CONCLUSIONS
These findings in two large groups suggest that future investigations should focus on other candidate genes and may support the view that MHC-encoded susceptibility to chronic HCV infection may be determined by MHC class II rather than MHC class III genes.
Constantini
Patricia K
PK
Institute of Liver Studies, King's College Hospital, London SE5 9RS, UK.
Wawrzynowicz-Syczewska
Marta
M
Clare
Michael
M
Boron-Kaczmarska
Anna
A
McFarlane
Ian G
IG
Cramp
Mathew E
ME
Donaldson
Peter T
PT
D000293:Adolescent; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019562:Viral Load; D014766:Viremia / Q000235:genetics* / Q000276:immunology
D016207:Cytokines; D016898:Interferon-alpha; D007375:Interleukin-1; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10