title: Contribution of genes for killer cell immunoglobulin-like receptors (KIR) to the susceptibility to chronic hepatitis C virus infection and to viremia.
abstract: BACKGROUND
  Natural killer (NK) cells are an important element of innate immunity against viruses, although their numbers decrease in the liver during chronic HCV infection. NK cells express a large panel of inhibitory and activating receptors. The most polymorphic of these are killer cell immunoglobulin-like receptors (KIRs) which are encoded by multiple genes that may be present or absent in given individuals depending on their genotype. This variability results in differential susceptibility to viral infections and diseases, including HCV infection and its consequences.
  
  
  OBJECTIVE
  The aim of this study was to test whether chronical infection with HCV and the viremia levels are associated with any KIR gene in the Polish population. We typed 301 chronically HCV-infected patients and 425 non-infected healthy individuals for the presence or absence of KIR genes and their ligands, HLA-C C1 and C2 groups as well as HLA-B and HLA-A Bw4-positive alleles.
  
  
  RESULTS
  We found that males, but not females, possessing KIR2DS2 and KIR2DL2 genes had a 1.7 higher probability to become chronically HCV-infected than males negative for these genes (p=0.0213). In accord with this, centromeric B region, containing KIR2DS2 and KIR2DL2 genes, was also associated with chronic HCV infection in males. In addition, patients of both genders possessing KIR2DS3 but not KIR2DS5 gene exhibited, on average, 2.6 lower level of viremia than HCV-infected individuals with other genotypes (p=0.00282). This was evident in those infected at a young age. KIR2DS3-positive patients also had lower mean levels of bilirubin than KIR2DS3-negative ones (p=0.02862).
  
  
  CONCLUSIONS
  Our results suggest a contribution of the KIR2DS2 and KIR2DL2 genes (cenB haplotype) to the susceptibility to chronic HCV infection, and an association of the KIR2DS3 gene in the absence of KIR2DS5 with low viremia levels.
authors: Laboratory of Immunogenetics and Tissue Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. Electronic address: pkusnier@iitd.pan.wroc.pl.
authors: Piotr
authors: P
authors: Kuśnierczyk
authors: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors: Iwona
authors: I
authors: Mozer-Lisewska
authors: Laboratory of Virology, Department of Immunology of Infectious Diseases, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors: Katarzyna
authors: K
authors: Zwolińska
authors: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors: Arleta Elżbieta
authors: AE
authors: Kowala-Piaskowska
authors: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors: Maciej
authors: M
authors: Bura
authors: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors: Iwona
authors: I
authors: Bereszyńska
authors: Chair and Department of Infectious Diseases, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors: Anna
authors: A
authors: Pauli
authors: Chair of Clinical Immunology, Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
authors: Jan
authors: J
authors: Żeromski
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D011044:Poland; D054340:Receptors, KIR / Q000235:genetics*; D012737:Sex Factors; D014766:Viremia / Q000235:genetics
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D054340:Receptors, KIR
keywords: Chronic infection; Genetics; Hepatitis C virus; Killer cell immunoglobulin-like receptors; Viremia