Natural killer cell receptor and HLA-C gene polymorphisms among patients with hepatitis C: a comparison between sustained virological responders and non-responders.
OBJECTIVE
Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy.


METHODS
We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits.


RESULTS
We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P<0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001).


CONCLUSIONS
Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.
Carneiro
Valdirene Leão
VL
Postgraduate Program in Immunology, Health Sciences Institute (ICS), Federal University of Bahia, Salvador, Bahia, Brazil.
Lemaire
Denise C
DC
Bendicho
Maria Teresita
MT
Souza
Sabrina L
SL
Cavalcante
Lourianne Nascimento
LN
Angelo
Ana Luisa
AL
Freire
Songeli Menezes
SM
Mendes
Carlos Maurício Cardeal
CM
Santana
Nelma
N
Lyra
Luiz G Costa
LG
Lyra
André Castro
AC
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D015236:HLA-C Antigens / Q000187:drug effects / Q000235:genetics*; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D054346:Receptors, KIR2DL5 / Q000187:drug effects / Q000235:genetics*; D055607:Receptors, Natural Killer Cell / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012254:Ribavirin / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D015236:HLA-C Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D054346:Receptors, KIR2DL5; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a