Interleukin 18 promoter variants (-137G>C and -607C>A) in patients with chronic hepatitis C: association with treatment response.
BACKGROUND
Recently, two functional IL18 promoter variants, -607C>A (rs1946518) and -137G>C (rs187238), were associated with viral clearance in patients with hepatitis C. The present study focused on their relevance for treatment response.


METHODS
Seven hundred fifty-seven chronically infected European patients and 791 controls were enrolled in the study. IL18 genotyping was performed by allele-specific PCR. Liver histology was available in 67.9%.


RESULTS
Genotype and allele frequencies were equally distributed in patients and controls. No significant association with various disease characteristics was observed. However, when comparing patients with sustained virological response (SR) and non-SR, statistically significant associations were found for both variants (p = 0.0416 and p = 0.0274, respectively). In viral genotype 1, the -607A allele was positively associated with treatment response (p = 0.0190; OR 1.537; 95% CI, 1.072-2.205) and the -137G allele with a higher rate of nonresponse (p = 0.0302; OR 1.524; 95% CI, 1.040-2.233).


CONCLUSIONS
The association of IL18 variants with treatment response in genotype 1 hepatitis C patients implies a predictive and modifying role of these genetic variants.
Haas
Stephan L
SL
Department of Medicine II, Medical Faculty at Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Weiss
Christel
C
Bugert
Peter
P
Gundt
Jutta
J
Witt
Heiko
H
Singer
Manfred V
MV
Berg
Thomas
T
Böcker
Ulrich
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000276:immunology* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000276:immunology; D012367:RNA, Viral / Q000032:analysis; D012254:Ribavirin / Q000008:administration & dosage; D016896:Treatment Outcome
D016898:Interferon-alpha; D020382:Interleukin-18; D012367:RNA, Viral; D012254:Ribavirin