Diversity of killer cell immunoglobulin-like receptor (KIR) genotypes and KIR2DL2/3 variants in HCV treatment outcome.

Abstract

The aim of this study was to analyse the distribution of KIR haplotypes and the KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the influence on the response to pegylated interferon plus ribavirin classical treatment. The alleles study of previously associated KIR2DL2/3 showed that KIR2DL2*001 was more frequent in non-SVR (NSVR) (42.2% vs. 27.5%, p<0.05) and KIR2DL3*001 was associated with sustained viral response (SVR) (41.6% vs. 61.2%, p<0.005). The KIR2DL3*001-HLA-C1 association was also significant (24.5% vs. 45.7%, p<0.001). From the frequencies of KIR obtained, 35 genotypes were assigned on the basis of previous studies. The centromeric A/A genotype was more frequent in SVR (44.1% vs. 34.5%, p<0.005) and the centromeric B/B genotype was found to be significantly more frequent in NSVR (20.9% vs. 11.2%, p<0.001). The logic regression model showed the importance of KIR genes in predicting the response to combined treatment, since the positive predictive value (PPV) was improved (from 55.9% to 75.3%) when the analysis of KIR was included in addition to the IFNL3 rs12979860 polymorphism. The study of KIR receptors may be a powerful tool for predicting the combined treatment response in patients with chronic HCV infection in association with the determination of IFNL3 polymorphism.

• Authors: Jose Ramón Vidal-Castiñeira, Antonio López-Vázquez, Jesús Martínez-Borra, Pablo Martínez-Camblor, Jesús Prieto, Rosario López-Rodríguez, Paloma Sanz-Cameno, Juan de la Vega, Luis Rodrigo, Rosa Pérez-López, Ramón Pérez-Álvarez, Carlos López-Larrea
• Journal: PloS one (PLoS One) Vol. 9 Issue 6 Pg. e99426 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24927414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• IFNL3 protein, human
• Interferon-alpha
• Interleukins
• KIR2DL2 protein, human
• KIR2DL3 protein, human
• Receptors, KIR2DL2
• Receptors, KIR2DL3
• Ribavirin
• Interferons

Topics

• Antiviral Agents (therapeutic use)
• Drug Therapy, Combination
• Genotype
• Haplotypes
• Hepacivirus (drug effects)
• Hepatitis C, Chronic (drug therapy, genetics, virology)
• Humans
• Interferon-alpha (therapeutic use)
• Interferons
• Interleukins (genetics)
• Killer Cells, Natural (immunology)
• Logistic Models
• Polymorphism, Single Nucleotide
• Receptors, KIR2DL2 (genetics)
• Receptors, KIR2DL3 (genetics)
• Ribavirin (therapeutic use)
• Treatment Outcome