Influence of interleukin 12B (IL12B) polymorphisms on spontaneous and treatment-induced recovery from hepatitis C virus infection.
OBJECTIVE
Interleukin-12 (IL-12) governs the Th1-type immune response, affecting the spontaneous and treatment-induced recovery from HCV-infection. We investigated whether the IL12B polymorphisms within the promoter region (4 bp insertion/deletion) and the 3'-UTR (1188-A/C), which have been reported to influence IL-12 synthesis, are associated with the outcome of HCV infection.


METHODS
We analyzed 186 individuals with spontaneous HCV clearance, 501 chronically HCV infected patients, and 217 healthy controls. IL12B 3'-UTR and promoter genotyping was performed by Taqman-based assays with allele-specific oligonucleotide probes and PCR-based allele-specific DNA-amplification, respectively.


RESULTS
The proportion of IL12B promoter and 3'-UTR genotypes did not differ significantly between the different cohorts. However, HCV genotype 1-infected patients with high baseline viremia carrying the IL12B 3'-UTR 1188-C-allele showed significantly higher sustained virologic response (SVR) rates (25.3% vs. 46% vs. 54.5% for A/A, A/C and C/C) due to reduced relapse rates (24.2% vs. 12% vs. zero % for A/A, A/C and C/C).


CONCLUSIONS
IL12B 3'-UTR 1188-C-allele carriers appear to be capable of responding more efficiently to antiviral combination therapy as a consequence of a reduced relapse rate. No association of IL12B polymorphisms and self-limited HCV infection could be demonstrated.
Charité, Campus Virchow-Klinikum, Medizinische Klinik mit Schwerpunkt, Hepatologie und Gastroenterologie, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Tobias
T
Mueller
Andreas
A
Mas-Marques
Christoph
C
Sarrazin
Manfred
M
Wiese
Juliane
J
Halangk
Heiko
H
Witt
Golo
G
Ahlenstiel
Ulrich
U
Spengler
Uwe
U
Goebel
Bertram
B
Wiedenmann
Eckart
E
Schreier
Thomas
T
Berg
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006579:Heterozygote; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012074:Remission Induction; D012075:Remission, Spontaneous; D012720:Severity of Illness Index
D020413:3' Untranslated Regions; D000998:Antiviral Agents; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D018664:Interleukin-12