Skip to main content
SpringerLink
Log in

Frequency of interleukin 28B rs12979860 C>T variants in Filipino patients chronically infected with hepatitis B virus

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Hepatitis B virus (HBV) is one of the most prevalent viral infections worldwide. Nearly 400 million individuals are chronic carriers of HBV. The aim of the present study was to determine the frequency of human interleukin 28B (IL28B) variants among treatment naive Filipino patients clinically diagnosed with chronic hepatitis B (CHB), and to compare the IL28B frequency distribution with various ethnic populations. Fifty-seven CHB patients and 43 normal controls were enrolled in this study. Real-time PCR was performed using the TaqMan genotyping assay for IL28B rs12979860. The allelic frequencies among normal controls were 0.94 and 0.06 for the IL28B rs12979860 C and T alleles, respectively. Eighty-eight percent were identified as homozygous for the IL28B C/C genotype and 12 % were identified as heterozygous for the IL28B C/T genotype. Among CHB patients, the allelic frequencies were 0.90 for the IL28B C allele and 0.10 for the IL28B T allele. No IL28B T/T genotype was observed between the two groups. No significant difference in the distribution of IL28B genotypes was observed between normal controls and CHB patients. Allelic frequencies of IL28B among Filipinos were similar with other Asian populations but significantly different from Caucasians. The frequency of rs12979860 C>T variants among Filipino CHB patients has not yet been reported. These data provided new insight into the geographical frequency distribution of IL28B variants. Further studies are needed to determine the possible association between IL28B variants and response to pegylated-interferon-α plus ribavirin combination therapy among Filipino patients chronically infected with HBV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bell SJ, Lau A, Thompson A, Watson KJ, Demediuk B, Shaw G, Chen RY, Ayres A, Yuen L, Bartholomeusz A, Locarnini SA, Desmond PV (2005) Chronic hepatitis B: recommendations for therapy based on the natural history of disease in Australian patients. J Clin Virol 32:122–127

    Article  CAS  PubMed  Google Scholar 

  2. Lee IC, Lin CH, Huang YH, Huo TI, Su CW, Hou MC, Huang HC, Lee KC, Chan CC, Lin MW, Lin HC, Lee SD (2013) IL28B polymorphism correlates with active hepatitis in patients with HBeAg-negative chronic hepatitis B. PLoS One 8:e58071. doi:10.1371/journal.pone.0058071

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Wong SN, Ong JP, Labio ME, Cabahug OT, Daez ML, Valdellon EV, Sollano JD Jr, Arguillas MO (2013) Hepatitis B infection among adults in the Philippines: a national seroprevalence study. World J Hepatol 5:214–219. doi:10.4254/wjh.v5.i4.214

    PubMed Central  PubMed  Google Scholar 

  4. Li W, Jiang Y, Jin Q, Shi X, Jin J, Gao Y, Pan Y, Zhang H, Jiang J, Niu J (2011) Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population. Liver Int 31:1118–1126. doi:10.1111/j.1478-3231.2011.02507.x

    Article  CAS  PubMed  Google Scholar 

  5. Chen J, Wang L, Li Y, Cai B, Fu Y, Liao Y, Zhang J (2012) Association analysis between SNPs in IL28B gene and the progress of hepatitis B infection in Han Chinese. PLoS One 7:e50787. doi:10.1371/journal.pone.0050787

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Hayashi K, Katano Y, Kuzuya T, Tachi Y, Honda T, Ishigami M, Itoh A, Hirooka Y, Ishikawa T, Nakano I, Urano F, Yoshioka K, Toyoda H, Kumada T, Goto H (2012) Prevalence of hepatitis C virus genotype 1a in Japan and correlation of mutations in the NS5A region and single nucleotide polymorphism of interleukin 28B with the response to combination therapy with pegylated-interferon-alpha 2b and ribavirin. J Med Virol 84:438–444. doi:10.1002/jmv.23207

    Article  CAS  PubMed  Google Scholar 

  7. Ren S, Lu J, Du X, Huang Y, Ma L, Huo H, Chen X, Wei L (2012) Genetic variation in IL28B is associated with the development of hepatitis B-related hepatocellular carcinoma. Cancer Immunol Immunother 61:1433–1439. doi:10.1007/s00262-012-1203-y

    Article  CAS  PubMed  Google Scholar 

  8. Kim SU, Song KJ, Chang HY, Shin EC, Park JY, Kim Do Y, Han KH, Chon CY, Ahn SH (2013) Association between IL28B polymorphisms and spontaneous clearance of hepatitis B virus infection. PLoS One 8:e69166. doi:10.1371/journal.pone.0069166

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Galmozzi E, Viganò M, Lampertico P (2014) Systematic review with meta-analysis: do interferon lambda 3 polymorphisms predict the outcome of interferon-therapy in hepatitis B infection? Aliment Pharmacol Ther 39:569–578. doi:10.1111/apt.12631

    Article  CAS  PubMed  Google Scholar 

  10. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:399–401. doi:10.1038/nature08309

    Article  CAS  PubMed  Google Scholar 

  11. Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Müller T, Bahlo M, Stewart GJ, Booth DR, George J (2009) IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41:1100–1104. doi:10.1038/ng.447

    Article  CAS  PubMed  Google Scholar 

  12. Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M (2009) Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 41:1105–1109. doi:10.1038/ng.449

    Article  CAS  PubMed  Google Scholar 

  13. Guo X, Yang G, Yuan J, Ruan P, Zhang M, Chen X, Zhou B (2013) Genetic variation in interleukin 28B and response to antiviral therapy in patients with dual chronic infection with hepatitis B and C viruses. PLoS One 8:e77911. doi:10.1371/journal.pone.0077911

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Martin MP, Qi Y, Goedert JJ, Hussain SK, Kirk GD, Hoots WK, Buchbinder S, Carrington M, Thio CL (2010) IL28B polymorphism does not determine outcomes of hepatitis B virus or HIV infection. J Infect Dis 202:1749–1753. doi:10.1086/657146

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Peng LJ, Guo JS, Zhang Z, Shi H, Wang J, Wang JY (2012) IL28B rs12979860 polymorphism does not influence outcomes of hepatitis B virus infection. Tissue Antigens 79:302–305. doi:10.1111/j.1399-0039.2011.01835.x

    Article  CAS  PubMed  Google Scholar 

  16. Holmes JA, Nguyen T, Ratnam D, Heerasing NM, Tehan JV, Bonanzinga S, Dev A, Bell S, Pianko S, Chen R, Visvanathan K, Hammond R, Iser D, Rusli F, Sievert W, Desmond PV, Bowden DS, Thompson AJ (2013) IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-α. J Gastroenterol Hepatol 28:861–866. doi:10.1111/jgh.12110

    Article  CAS  PubMed  Google Scholar 

  17. Kandemir Ö, Fidancı SB, Demir N, Görür A, Tamer L (2013) Chronic hepatitis B and IL28B rs12979860 polymorphism: preliminary study. Mol Biol Rep 40:6189–6194. doi:10.1007/s11033-013-2730-0

    Article  CAS  PubMed  Google Scholar 

  18. Lee DH, Cho Y, Seo JY, Kwon JH, Cho EJ, Jang ES, Kwak MS, Cheong JY, Cho SW, Lee JH, Yu SJ, Yoon JH, Lee HS, Kim CY, Shin HD, Kim YJ (2013) Polymorphisms near interleukin 28B gene are not associated with hepatitis B virus clearance, hepatitis B e antigen clearance and hepatocellular carcinoma occurrence. Intervirology 56:84–90. doi:10.1159/000342526

    Article  CAS  PubMed  Google Scholar 

  19. Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, Kidd J, Kidd K, Khakoo SI, Alexander G, Goedert JJ, Kirk GD, Donfield SM, Rosen HR, Tobler LH, Busch MP, McHutchison JG, Goldstein DB, Carrington M (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461:798–801. doi:10.1038/nature08463

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Hayes CN, Imamura M, Aikata H, Chayama K (2012) Genetics of IL28B and HCV response to infection and treatment. Nat Rev Gastroenterol Hepatol 9:406–417. doi:10.1038/nrgastro.2012.101

    Article  CAS  PubMed  Google Scholar 

  21. Younossi ZM, Birerdinc A, Estep M, Stepanova M, Afendy A, Baranova A (2012) The impact of IL28B genotype on the gene expression profile of patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin. J Transl Med 10:25. doi:10.1186/1479-5876-10-25

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Zeng GB, Wen SJ, Wang ZH, Yan L, Sun J, Hou JL (2004) A novel hepatitis B virus genotyping system by using restriction fragment length polymorphism patterns of S gene amplicons. World J Gastroenterol 10:3132–3136

    CAS  PubMed  Google Scholar 

  23. Baclig MO, Alvarez MR, Gopez-Cervantes J, Natividad FF (2014) Unique surface gene variants of hepatitis B virus isolated from patients in the Philippines. J Med Virol 86:209–216. doi:10.1002/jmv.23717

    Article  CAS  PubMed  Google Scholar 

  24. Fabris C, Falleti E, Cussigh A, Bitetto D, Fontanini E, Bignulin S, Cmet S, Fornasiere E, Fumolo E, Fangazio S, Cerutti A, Minisini R, Pirisi M, Toniutto P (2011) IL-28B rs12979860 C/T allele distribution in patients with liver cirrhosis: role in the course of chronic viral hepatitis and the development of HCC. J Hepatol 54:716–722. doi:10.1016/j.jhep.2010.07.019

    Article  CAS  PubMed  Google Scholar 

  25. Rodriguez S, Gaunt TR, Day INM (2009) Hardy-Weinberg Equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol 169:505–514. doi:10.1093/aje/kwn359

    Article  PubMed Central  PubMed  Google Scholar 

  26. Akkarathamrongsin S, Thong VD, Payungporn S, Poovorawan K, Prapunwattana P, Poovorawan Y, Tangkijvanich P (2014) IFNL3 (IL28B) and IFNL4 polymorphisms are associated with treatment response in Thai patients infected with HCV genotype 1, but not with genotypes 3 and 6. J Med Virol. doi:10.1002/jmv.23957

    PubMed  Google Scholar 

  27. Gélinas JF, Fabre T, Willems P, Leung RC, George J, Willems B, Bruneau J, Shoukry NH (2013) IL28B SNP screening and distribution in the French Canadian population using a rapid PCR-based test. Immunogenetics 65:397–403. doi:10.1007/s00251-013-0688-7

    Article  PubMed Central  PubMed  Google Scholar 

  28. Montes-Cano MA, García-Lozano JR, Abad-Molina C, Romero-Gómez M, Barroso N, Aguilar-Reina J, Núñez-Roldán A, González-Escribano MF (2010) Interleukin-28B genetic variants and hepatitis virus infection by different viral genotypes. Hepatology 52:33–37. doi:10.1002/hep.23624

    Article  CAS  PubMed  Google Scholar 

  29. Roberts SK, Mitchell J, Leung R, Booth D, Bollipo S, Ostapowicz G, Sloss A, McCaughan GW, Dore GJ, Thompson A, Crawford DH, Sievert W, Weltman M, Cheng W, George J, Network Australian Liver Association Clinical Research (2014) Distribution of interferon lambda-3 gene polymorphisms in Australian patients with previously untreated genotype 1 chronic hepatitis C: analysis from the PREDICT and CHARIOT studies. J Gastroenterol Hepatol 29:179–184. doi:10.1111/jgh.12424

    Article  CAS  PubMed  Google Scholar 

  30. Kimball P, Elswick RK, Shiffman M (2001) Ethnicity and cytokine production gauge response of patients with hepatitis C to interferon-alpha therapy. J Med Virol 65:510–516

    Article  CAS  PubMed  Google Scholar 

  31. Moreira S, Garcia RFL, Gutberlet A, Bertol BC, Ferreira LE, de Souza Leite Pinho M, de França PHC (2012) A straightforward genotyping of the relevant IL28B SNPs for the prediction of hepatitis C treatment outcome. J Virol Methods 184:93–97. doi:10.1016/j.jviromet.2012.05.024

    Article  CAS  PubMed  Google Scholar 

  32. Martinot-Peignoux M, Lapalus M, Laouénan C, Lada O, Netto-Cardoso AC, Boyer N, Ripault MP, Carvalho-Filho R, Asselah T, Marcellin P (2013) Prediction of disease reactivation in asymptomatic hepatitis B e antigen-negative chronic hepatitis B patients using baseline serum measurements of HBsAg and HBV-DNA. J Clin Virol 58:401–417. doi:10.1016/j.jcv.2013.08.010

    Article  CAS  PubMed  Google Scholar 

  33. Fonseca-Coronado S, Vaughan G, Cruz-Rivera MY, Carpio-Pedroza JC, Ruiz-Tovar K, Ruiz-Pacheco JA, Escobar-Gutiérrez A (2011) Interleukin-28B genotyping by melt-mismatch amplification mutation assay PCR analysis using single nucleotide polymorphisms rs12979860 and rs8099917 a useful tool for prediction of therapy response in hepatitis C patients. Clin Microbiol 49:2706–2710. doi:10.1128/JCM.00877-11

    Article  CAS  Google Scholar 

  34. Wu X, Xin Z, Zhu X, Pan L, Li Z, Li H, Liu Y (2012) Evaluation of susceptibility locus for response to interferon-α based therapy in chronic hepatitis B patients in Chinese. Antiviral Res 93:297–300. doi:10.1016/j.antiviral.2011.12.009

    Article  CAS  PubMed  Google Scholar 

  35. Kani S, Tanaka Y, Matsuura K, Watanabe T, Yatsuhashi H, Orito E, Inose K, Motojuku N, Wakimoto Y, Mizokami M (2012) Development of new IL28B genotyping method using Invader Plus assay. Microbiol Immunol 56:318–323. doi:10.1111/j.1348-0421.2012.00439.x

    Article  CAS  PubMed  Google Scholar 

  36. Rao H, Wei L, Lopez-Talavera JC, Shang J, Chen H, Li J, Xie Q, Gao Z, Wang L, Wei J, Jiang J, Sun Y, Yang R, Li H, Zhang H, Gong Z, Zhang L, Zhao L, Dou X, Niu J, You H, Chen Z, Ning Q, Gong G, Wu S, Ji W, Mao Q, Tang H, Li S, Wei S, Sun J, Jiang J, Lu L, Jia J, Zhuang H (2014) Distribution and clinical correlates of viral and host genotypes in Chinese patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol 29:545–553. doi:10.1111/jgh.12398

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Stättermayer AF, Scherzer T, Beinhardt S, Rutter K, Hofer H, Ferenci P (2014) Review article: genetic factors that modify the outcome of viral hepatitis. Aliment Pharmacol Ther 39:1059–1070. doi:10.1111/apt.12717

    Article  PubMed  Google Scholar 

  38. Yu ML, Dai CY, Huang CF, Lee JJ, Yeh ML, Yeh SM, Kuo HT, Huang JF, Chang JM, Chen HC, Juo SH, Hwang SJ, Chuang WL, FORMOSA-LIKE group (2014) High hepatitis B virus surface antigen levels and favorable interleukin 28B genotype predict spontaneous hepatitis C virus clearance in uremic patients. J Hepatol 60:253–259. doi:10.1016/j.jhep.2013.09.023

    Article  CAS  PubMed  Google Scholar 

  39. Sonneveld MJ, Wong VW, Woltman AM, Wong GL, Cakaloglu Y, Zeuzem S, Buster EH, Uitterlinden AG, Hansen BE, Chan HL, Janssen HL (2012) Polymorphisms near IL28B and serologic response to peginterferon in HBeAg-positive patients with chronic hepatitis B. Gastroenterology 142:513–520. doi:10.1053/j.gastro.2011.11.025

    Article  CAS  PubMed  Google Scholar 

  40. Al-Qahtani AA, Al-Anazi MR, Abdo AA, Sanai FM, Al-Hamoudi WK, Alswat KA, Al-Ashgar HI, Khalaf NZ, Viswan NA, Al Ahdal MN (2013) Genetic variation in interleukin 28B and correlation with chronic hepatitis B virus infection in Saudi Arabian patients. Liver Int. doi:10.1111/liv.12347

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a research grant to the St. Luke’s Liver Diseases Study Group (Project No. 12-002c) through the Research and Biotechnology, St. Luke’s Medical Center-Quezon City.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Research and Biotechnology, St. Luke’s Medical Center, 279 E. Rodriguez Sr. Blvd., 1112, Quezon City, Philippines

    Michael O. Baclig, Karen G. Reyes, Cynthia A. Mapua & Filipinas F. Natividad

  2. Liver Disease and Transplant Center, St. Luke’s Medical Center, 279 E. Rodriguez Sr. Blvd., 1112, Quezon City, Philippines

    Juliet Gopez-Cervantes

Authors
  1. Michael O. Baclig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen G. Reyes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cynthia A. Mapua
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Juliet Gopez-Cervantes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Filipinas F. Natividad
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

The St. Luke’s Liver Diseases Study Group

Corresponding author

Correspondence to Michael O. Baclig.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baclig, M.O., Reyes, K.G., Mapua, C.A. et al. Frequency of interleukin 28B rs12979860 C>T variants in Filipino patients chronically infected with hepatitis B virus. Mol Biol Rep 42, 673–679 (2015). https://doi.org/10.1007/s11033-014-3814-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3814-1

Keywords

Search

Navigation