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Distribution of IL28B and IL10 polymorphisms as genetic predictors of treatment response in Pakistani HCV genotype 3 patients

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Abstract

There are over 10 million hepatitis C virus (HCV)-infected patients in Pakistan. For these patients, a combination of interferon with ribavirin is the most economical and easily available treatment. Single-nucleotide polymorphisms in interleukin genes have been reported to be associated with the pathogenesis and clearance of HCV, and sustained virologic response (SVR). An interleukin 28B (IL28B) gene polymorphism has been shown to modify treatment outcomes, but the effects of interleukin 10 (IL10) polymorphisms have not been previously assessed in the Pakistani population. The present study was conducted with 302 subjects categorized into two groups: 100 healthy volunteers (Group I) and 202 patients with chronic HCV (Group II). Patients within Group II were further divided into two subgroups according to therapeutic response: SVR (responders = 132) and NR (non-responders/relapsers = 70). IL28B (rs8099917, rs12979860) and IL10 (rs1800872, rs1800871, rs1800896) gene polymorphisms were studied in all subjects. A significant difference in the distribution of IL28B rs12979860C/T genotypes between the two groups (p<0.05) was observed, while of the three IL10 polymorphisms, a significant difference was only shown for rs1800896 A/G. Haplotype analysis (IL28B and IL10) showed a significant association of TTGTC and TTGTA when comparing the groups. There was a strong association of the favorable alleles rs8099917T and rs12979860C in the SVR group as compared with the NR group (p<0.05), and rs1800896 also showed an association with the SVR group as compared to the NR group (p<0.004). Haplotype analysis showed significant associations when comparing the SVR and NR subgroups, i.e. TCATC (p=0.009), TTGTA (p=0.005), TCATA (p<0.0005), TCACA (p=0.002), GTGCC (p=0.002) and TCGTC (p=0.005). IL28B (rs8099917 and rs12979860) and IL10 (rs1800896) polymorphisms alone, or in combination, are good predictors of therapeutic response in HCV-3a patients.

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Acknowledgements

We are grateful to all the hospital and laboratory staff, and patients who participated in this study.

Funding

The research was supported by Higher Education Commission Pakistan start-up research grant (PM-IPFP/HRD/HEC/2011/2257).

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Author notes

  1. Humaira Naeemi and Rabia Aslam equally contributed.

Authors and Affiliations

  1. Department of Immunology, University of Health Sciences, Lahore, Pakistan

    Humaira Naeemi, Rabia Aslam, Muhammad Aiman Shahzad & Saba Khaliq

  2. Department of Physiology and Cell Biology, University of Health Sciences, Khayaban-e-Jamia Punjab, Lahore, Pakistan

    Syed Mohsin Raza & Saba Khaliq

  3. Department of Zoology, Lahore College University, Lahore, Pakistan

    Humaira Naeemi & Shagufta Naz

  4. Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan

    Sobia Manzoor

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  1. Humaira Naeemi
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Correspondence to Saba Khaliq.

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All authors declare no conflict of interest.

Ethical approval

The research was approved by the Institutional ethical and the review committee accordingly to the Helsinki Declaration and its later amendments.

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Informed consents were taken from all the subjects i.e., Patients and healthy controls before start of sample collection.

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Handling Editor: Michael A. Purdy.

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Naeemi, H., Aslam, R., Raza, S.M. et al. Distribution of IL28B and IL10 polymorphisms as genetic predictors of treatment response in Pakistani HCV genotype 3 patients. Arch Virol 163, 997–1008 (2018). https://doi.org/10.1007/s00705-018-3711-3

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  • DOI: https://doi.org/10.1007/s00705-018-3711-3

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