title: Interleukin 6 promoter polymorphisms influence the outcome of chronic hepatitis C.
abstract: Host genetic variation may affect the outcome of chronic viral hepatitides, favoring viral clearance and/or modulating the inflammatory response to persistent infection. Our aims were to assess whether interleukin 6 (IL-6) promoter polymorphisms are associated with chronic hepatitis C virus (HCV) infection and to clarify the role of IL-6 haplotypes in facilitating progressive disease. The study included 424 Italian patients (233 males, median age 53 years) affected by HCV chronic infection. IL6 -1363, -597, -572, -174, and +2954 polymorphic loci were assayed by means of restriction fragment length polymorphism. Three hundred forty-four healthy Italian blood donors (245 males, median age 50 years) served as controls. Comparing patients and controls analysis of molecular variance was highly significant (p < 0.0001); at a locus by locus approach, the frequencies of minor alleles in the -1363 (p < 0.02), -597 (p < 0.02), and -174 (p < 0.01) polymorphisms were confirmed to be less represented in patients than in controls. Carrying the wild-type G allele at the -597 and -174 loci identified an unfavorable haplotype; carrying the minor allele in one/both loci identified an indifferent/favorable haplotype. Male patients carrying two unfavorable haplotypes had the highest adjusted mean ± standard error Ishak staging score (3.56 ± 0.19), while females carrying one or no unfavorable haplotypes had the lowest (2.69 ± 0.21); the remaining patients had an intermediate value (3.12 ± 0.13, p < 0.01). In conclusion, IL-6 promoter polymorphisms influence the development of chronic HCV infection. With the permissive effect of male gender, haplotypes represented by the wild-type allele for -597 and -174 loci appear to favor a worse evolution of the disease.
authors.affiliation: Laboratory Medicine, University of Udine, Udine, Italy.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Cussigh
authors.forename: Edmondo
authors.initials: E
authors.lastname: Falleti
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabris
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.forename: Sara
authors.initials: S
authors.lastname: Cmet
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Fontanini
authors.forename: Sara
authors.initials: S
authors.lastname: Bignulin
authors.forename: Ezio
authors.initials: E
authors.lastname: Fornasiere
authors.forename: Elisa
authors.initials: E
authors.lastname: Fumolo
authors.forename: Rosalba
authors.initials: R
authors.lastname: Minisini
authors.forename: Mario
authors.initials: M
authors.lastname: Pirisi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D017931:DNA Primers; C508600:IL6 protein, human; D015850:Interleukin-6