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...

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Published in:	Journal of clinical immunology Vol. 29; no. 5; pp. 620 - 628
Main Authors:	Haas, Stephan L, Weiß, Christel, Bugert, Peter, Gundt, Jutta, Witt, Heiko, Singer, Manfred V, Berg, Thomas, Böcker, Ulrich
Format:	Journal Article
Language:	English
Published:	Boston Boston : Springer US 01-09-2009 Springer US Springer Nature B.V
Subjects:	Adolescent Adult Aged Aged, 80 and over Alleles Biomedical and Life Sciences Biomedicine Disease Progression Female Gene frequency Genetic diversity Genotype Genotype & phenotype Genotypes Genotyping Hepacivirus - drug effects Hepacivirus - immunology Hepacivirus - pathogenicity Hepatitis C Hepatitis C, Chronic - diagnosis Hepatitis C, Chronic - genetics Hepatitis C, Chronic - immunology Hepatitis C, Chronic - physiopathology Hepatitis C, Chronic - therapy Humans Immunology Infectious Diseases Interferon-alpha - administration & dosage Interleukin 18 Interleukin-18 - genetics Interleukin-18 - immunology Internal Medicine Liver Male Medical Microbiology Middle Aged Patients Polymerase chain reaction Polymorphism, Genetic Prognosis Promoter Regions, Genetic - immunology Promoters Ribavirin - administration & dosage RNA, Viral - analysis Statistical analysis Treatment Outcome genetic alterations Hepatitis C treatment outcome interleukin 18 antiviral therapy
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Abstract	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.
AbstractList	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. 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. BackgroundRecently, 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.MethodsSeven 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%.ResultsGenotype 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).ConclusionsThe association of IL18 variants with treatment response in genotype 1 hepatitis C patients implies a predictive and modifying role of these genetic variants. 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. 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%. 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). The association of IL18 variants with treatment response in genotype 1 hepatitis C patients implies a predictive and modifying role of these genetic variants. Issue Title: Special Issue on Osteoimmunology; Editor: Dr. Sudhir Gupta, MD, Ph. D, MACP 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. 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%. 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). The association of IL18 variants with treatment response in genotype 1 hepatitis C patients implies a predictive and modifying role of these genetic variants.
Author	Gundt, Jutta Böcker, Ulrich Weiß, Christel Haas, Stephan L Berg, Thomas Singer, Manfred V Witt, Heiko Bugert, Peter
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Snippet	Background Recently, two functional IL18 promoter variants, -607C>A (rs1946518) and -137G>C (rs187238), were associated with viral clearance in patients with... Background Recently, two functional IL18 promoter variants, −607C>A (rs1946518) and −137G>C (rs187238), were associated with viral clearance in patients with... Recently, two functional IL18 promoter variants, -607C>A (rs1946518) and -137G>C (rs187238), were associated with viral clearance in patients with hepatitis C.... Issue Title: Special Issue on Osteoimmunology; Editor: Dr. Sudhir Gupta, MD, Ph. D, MACP Recently, two functional IL18 promoter variants, -607C>A (rs1946518)... BackgroundRecently, two functional IL18 promoter variants, −607C>A (rs1946518) and −137G>C (rs187238), were associated with viral clearance in patients with... Background: Recently, two functional IL18 promoter variants, -607C>A (rs1946518) and -137G>C (rs187238), were associated with viral clearance in patients with...
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SubjectTerms	Adolescent Adult Aged Aged, 80 and over Alleles Biomedical and Life Sciences Biomedicine Disease Progression Female Gene frequency Genetic diversity Genotype Genotype & phenotype Genotypes Genotyping Hepacivirus - drug effects Hepacivirus - immunology Hepacivirus - pathogenicity Hepatitis C Hepatitis C, Chronic - diagnosis Hepatitis C, Chronic - genetics Hepatitis C, Chronic - immunology Hepatitis C, Chronic - physiopathology Hepatitis C, Chronic - therapy Humans Immunology Infectious Diseases Interferon-alpha - administration & dosage Interleukin 18 Interleukin-18 - genetics Interleukin-18 - immunology Internal Medicine Liver Male Medical Microbiology Middle Aged Patients Polymerase chain reaction Polymorphism, Genetic Prognosis Promoter Regions, Genetic - immunology Promoters Ribavirin - administration & dosage RNA, Viral - analysis Statistical analysis Treatment Outcome
Title	Interleukin 18 Promoter Variants (-137G>C and -607C>A) in Patients with Chronic Hepatitis C: Association with Treatment Response
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