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Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients

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Abstract

Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07–26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.

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Abbreviations

aOR:

Adjusted odds ratio

BMI:

Body mass index

cART:

Combination antiretroviral therapy

CD127 or IL7Rα:

α-Chain of the IL-7 receptor

DAAs:

New direct-acting antivirals

GT1/4:

Genotypes 1/4

GT2/3:

Genotypes 2/3

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

HOMA:

Homeostatic model assessment

HWE:

Hardy–Weinberg equilibrium

IL28B:

Interleukin 28B

IL-7:

Interleukin-7

IL7RA :

Gene of IL7Rα

LD:

Linkage disequilibrium

NA:

Not available due to a low number of patients in one of the groups

pegIFNα/ribavirin:

Pegylated interferon-alpha plus ribavirin

SNPs:

Single nucleotide polymorphisms

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Acknowledgements

The authors wish to thank the Spanish National Genotyping Center (CeGen) for providing the SNP genotyping services (http://www.cegen.org/).

Funding/support

This work has been supported by grants given by Fondo de Investigación de Sanidad en España (FIS) (Spanish Health Funds for Research) (grant numbers PI08/0738, PI11/00245, PI08/0928, and PI11/01556) and Fundación para la Investigación y la Prevención del Sida en España (FIPSE) (grant number 361020/10). This work has been (partially) funded by the RD12/0017/0024 and RD12/0017/0004 projects as part of the Plan Nacional R + D + I and cofinanced by ISCIII Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).

JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS; Refs INT10/009 and INT12/154). Moreover, DP-T, MG-F, MAJ-S and MG-A are supported by Instituto de Salud Carlos III (grant numbers CM12/00043, RD12/0017/0024, CD13/00012 and CD12/00442 respectively).

Conflict of interest

The authors do not have a commercial or other association that might pose a conflict of interest.

Author contributions

MG-F and SR performed all statistical analyses, interpretation of the data, and wrote the manuscript.

JB and SR participated in the study concept and design.

JB, TA-E, AC, CD, and FT participated in patient selection, collection of samples, and acquisition of data.

DP-T, MAJ-S, MG-A, SV, and VB participated in sample preparation, DNA isolation and genotyping pre-procedure, and contributed with critical revisions of the manuscript.

SR supervised the study.

All authors revised the manuscript from a draft by SR.

Author information

Authors and Affiliations

  1. Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda—Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain

    M. Guzmán-Fulgencio, D. Pineda-Tenor, M. A. Jiménez-Sousa, M. García-Álvarez, S. Vázquez, V. Briz & S. Resino

  2. Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain

    J. Berenguer, T. Aldámiz-Echevarria, A. Carrero, C. Diez & F. Tejerina

  3. Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain

    J. Berenguer, T. Aldámiz-Echevarria, A. Carrero, C. Diez & F. Tejerina

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  1. M. Guzmán-Fulgencio
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  2. J. Berenguer
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  3. D. Pineda-Tenor
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  5. M. García-Álvarez
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  6. T. Aldámiz-Echevarria
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  8. C. Diez
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  10. S. Vázquez
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  11. V. Briz
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  12. S. Resino
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Correspondence to S. Resino.

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Guzmán-Fulgencio, M., Berenguer, J., Pineda-Tenor, D. et al. Association between IL7RA polymorphisms and the successful therapy against HCV in HIV/HCV-coinfected patients. Eur J Clin Microbiol Infect Dis 34, 385–393 (2015). https://doi.org/10.1007/s10096-014-2245-1

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