title: KIR genes and their human leukocyte antigen ligands in the progression to cirrhosis in patients with chronic hepatitis C.
abstract: Natural killer (NK) cells play pivotal roles in immune responses against infection with viruses, such as hepatitis C virus (HCV), and killer cell immunoglobulin-like receptors (KIRs) are related to the activation and inhibition of NK cells. The aim of this study was to investigate the possibility that KIR genes and their human leukocyte antigen (HLA) ligands influence progression to cirrhosis in patients infected with genotype 1 of HCV. A total of 145 Brazilian patients with confirmed chronic hepatitis C grouped from F0 to F4 according to fibrosis progression to cirrhosis were evaluated. Genotyping of KIR and HLA genes was performed by polymerase chain reaction with sequence-specific oligonucleotide probes. The HLA-C2 KIR ligand was more frequent in patients than in healthy controls (74.5% vs 64.3%, p = 0.04, odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.03-2.52). Moreover, the HLA-C1C2 genotype was more frequent in patients with advanced fibrosis or cirrhosis (F3-F4 group) than in patients in the F0-F2 group (61.6% vs 44.7%, p = 0.06) and in the F4 group compared with the F0-F3 group (65.7% vs 46.7%, p = 0.05, OR = 2.19, 95% CI = 1.01-4.73). NK and KIR ligands may contribute to the development of liver damage in patients chronically infected by HCV.
authors.affiliation: Immunogenetics Laboratory, Department of Basic Sciences, Maringá State University, UEM, Maringá, Paraná, Brazil. amanda_vansan@hotmail.com
authors.forename: Amanda Vansan
authors.initials: AV
authors.lastname: Marangon
authors.forename: Giovanni Faria
authors.initials: GF
authors.lastname: Silva
authors.forename: Camila Fernanda Verdichio
authors.initials: CF
authors.lastname: de Moraes
authors.forename: Rejane Maria Tomasini
authors.initials: RM
authors.lastname: Grotto
authors.forename: Maria Inês de Moura Campos
authors.initials: MI
authors.lastname: Pardini
authors.forename: Dayse Sousa
authors.initials: DS
authors.lastname: de Pauli
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Sell
authors.forename: Jeane Eliete Laguila
authors.initials: JE
authors.lastname: Visentainer
authors.forename: Ricardo Alberto
authors.initials: RA
authors.lastname: Moliterno
mesh_terms: D000328:Adult; D001938:Brazil; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016174:Hepacivirus / Q000276:immunology* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008024:Ligands; D008099:Liver / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054340:Receptors, KIR / Q000819:agonists / Q000235:genetics*
chemical_list: D015236:HLA-C Antigens; D008024:Ligands; D054340:Receptors, KIR