Virus Genes

, Volume 53, Issue 4, pp 532–537 | Cite as

Filaggrin gene polymorphism associated with Epstein–Barr virus-associated tumors in China

  • Yang Yang
  • Wen Liu
  • Zhenzhen Zhao
  • Yan Zhang
  • Hua Xiao
  • Bing LuoEmail author


Mutations of filaggrin gene (FLG) have been identified as the cause of ichthyosis vulgaris, while recently FLG mutations were found to be associated with gastric cancer. This study aimed to investigate the association of filaggrin polymorphism with Epstein–Barr virus-associated tumors in China. A total of 200 patients with three types of tumors and 117 normal control samples were genotyped at three common FLG mutation loci (rs3126085, K4671X, R501X) by using Sequenom MassARRAY technique. The χ 2 test was used to evaluate the relationship between the mutation and the three kinds of tumors. A two-sided P value of <0.05 was considered statistically significant. The results showed that two single-nucleotide polymorphism (SNP) loci (rs3126085, K4671X) were significantly associated with nasopharyngeal carcinoma in genetic model. In addition, the two SNPs K4671X and rs3126085 were related to Epstein–Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), respectively. Furthermore, allele distributions in EBVaGC and EBVnGC were verified to be different in both SNP loci.


Filaggrin SNP Epstein–Barr virus Nasopharyngeal carcinoma Gastric carcinoma 



This research was supported by the National Natural Science Foundation of China (NSFC 81571995) and the Natural Science Foundation of Shandong Province (ZR2015HM069).

Author contributions

BL conceived the project and designed experiments. YY mainly conducted the experiments. WL, YZ, HX, ZZZ participated in performance of the experiments and the drafting of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no competing interests.

Ethical approval

This study was approved by the Medical Ethics Committee of the Medical College of Qingdao University.

Informed consent

Informed consents were received from all patients.


  1. 1.
    W. Henle, G. Henle, Bibl. Haematol. 36, 706 (1970)Google Scholar
  2. 2.
    M.S. Wu, C.T. Shun, C.C. Wu, T.Y. Hsu, M.T. Lin, M.C. Chang, H.P. Wang, J.T. Lin, Gastroenterology 118, 1031 (2000)CrossRefPubMedGoogle Scholar
  3. 3.
    H. Hausen, H. Schulte-Holthausen, G. Klein, W. Henle, G. Henle, P. Clifford, L. Santesson, Nature 228, 1056 (1970)CrossRefPubMedGoogle Scholar
  4. 4.
    M.A. Epstein, B.G. Achong, Y.M. Barr, Lancet 1, 702 (1964)CrossRefPubMedGoogle Scholar
  5. 5.
    N. Raab-Traub, K. Flynn, Cell 47, 883 (1986)CrossRefPubMedGoogle Scholar
  6. 6.
    C. Lara, V. Serra, C. Marzo, F. Valcuende, A. Castells, F.M. Bonilla-Musoles, Arch. Gynecol. Obstet. 255, 73 (1994)CrossRefPubMedGoogle Scholar
  7. 7.
    G. Mocsai, K. Gaspar, G. Nagy, B. Irinyi, A. Kapitany, T. Biro, E. Gyimesi, B. Toth, L. Marodi, A. Szegedi, Br. J. Dermatol. 170, 617 (2014)CrossRefPubMedGoogle Scholar
  8. 8.
    M. Manabe, M. Sanchez, T.T. Sun, B.A. Dale, Differentiation 48, 43 (1991)CrossRefPubMedGoogle Scholar
  9. 9.
    F.J. Smith, A.D. Irvine, A. Terron-Kwiatkowski, A. Sandilands, L.E. Campbell, Y. Zhao, H. Liao, A.T. Evans, D.R. Goudie, S. Lewis-Jones, G. Arseculeratne, C.S. Munro, A. Sergeant, G. O’Regan, S.J. Bale, J.G. Compton, J.J. DiGiovanna, R.B. Presland, P. Fleckman, W.H. McLean, Nat. Genet. 38, 337 (2006)CrossRefPubMedGoogle Scholar
  10. 10.
    T. Skaaby, L.L. Husemoen, T. Jorgensen, J.D. Johansen, T. Menne, P.B. Szecsi, S. Stender, P. Bager, J.P. Thyssen, A. Linneberg, PLoS ONE 9, e99437 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    J. Adnane, P. Gaudray, C.A. Dionne, G. Crumley, M. Jaye, J. Schlessinger, P. Jeanteur, D. Birnbaum, C. Theillet, Oncogene 6, 659 (1991)PubMedGoogle Scholar
  12. 12.
    X. Kuang, L. Sun, S. Liu, Z. Zhao, D. Zhao, S. Liu, B. Luo, Virol. Sin. 31, 306 (2016)CrossRefPubMedGoogle Scholar
  13. 13.
    A.C. Campos, E.F. Murta, M.A. Michelin, C. Reis, ISRN Obstet. Gynecol. 2012, 342075 (2012)PubMedPubMedCentralGoogle Scholar
  14. 14.
    M. Li, Q. Liu, J. Liu, R. Cheng, H. Zhang, H. Xue, Y. Bao, Z. Yao, J. Eur. Acad. Dermatol. Venereol. 27, 169 (2013)CrossRefPubMedGoogle Scholar
  15. 15.
    C. Shen, L. Liu, Z. Jiang, X. Zheng, L. Meng, X. Yin, J. Gao, Y. Sheng, J. Gao, Y. Li, F. Zhou, F. Xiao, L. Sun, Y. Cui, S. Yang, X. Zuo, X. Zhang, Mol. Genet. Genomics 290, 1493 (2015)CrossRefPubMedGoogle Scholar
  16. 16.
    C.N. Palmer, A.D. Irvine, A. Terron-Kwiatkowski, Y. Zhao, H. Liao, S.P. Lee, D.R. Goudie, A. Sandilands, L.E. Campbell, F.J. Smith, G.M. O’Regan, R.M. Watson, J.E. Cecil, S.J. Bale, J.G. Compton, J.J. DiGiovanna, P. Fleckman, S. Lewis-Jones, G. Arseculeratne, A. Sergeant, C.S. Munro, B. El Houate, K. McElreavey, L.B. Halkjaer, H. Bisgaard, S. Mukhopadhyay, W.H. McLean, Nat. Genet. 38, 441 (2006)CrossRefPubMedGoogle Scholar
  17. 17.
    A. Filipowska-Gronska, M. Werynska-Kalemba, A. Bozek, B. Filipowska, J. Zebracka-Gala, D. Rusinek, D. Kula, J. Jarzab, Postepy. Dermatol. Alergol. 33, 37 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    G. Khan, P.J. Coates, H.O. Kangro, G. Slavin, J. Clin. Pathol. 45, 616 (1992)CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    R. Pathmanathan, U. Prasad, G. Chandrika, R. Sadler, K. Flynn, N. Raab-Traub, Am. J. Pathol. 146, 1355 (1995)PubMedPubMedCentralGoogle Scholar
  20. 20.
    S.Q. Gan, O.W. McBride, W.W. Idler, N. Markova, P.M. Steinert, Biochemistry 29, 9432 (1990)CrossRefPubMedGoogle Scholar
  21. 21.
    S.Q. Gan, O.W. McBride, W.W. Idler, N. Markova, P.M. Steinert, Biochemistry 30, 5814 (1991)CrossRefPubMedGoogle Scholar
  22. 22.
    A. Sandilands, G.M. O’Regan, H. Liao, Y. Zhao, A. Terron-Kwiatkowski, R.M. Watson, A.J. Cassidy, D.R. Goudie, F.J. Smith, W.H. McLean, A.D. Irvine, J. Invest. Dermatol. 126, 1770 (2006)CrossRefPubMedGoogle Scholar
  23. 23.
    R. Gruber, A.R. Janecke, C. Fauth, G. Utermann, P.O. Fritsch, M. Schmuth, Eur. J. Hum. Genet. 15, 179 (2007)CrossRefPubMedGoogle Scholar
  24. 24.
    S.J. Brown, K. Kroboth, A. Sandilands, L.E. Campbell, E. Pohler, S. Kezic, H.J. Cordell, W.H. McLean, A.D. Irvine, J. Invest. Dermatol. 132, 98 (2012)CrossRefPubMedGoogle Scholar
  25. 25.
    L.D. Sun, F.L. Xiao, Y. Li, W.M. Zhou, H.Y. Tang, X.F. Tang, H. Zhang, H. Schaarschmidt, X.B. Zuo, R. Foelster-Holst, S.M. He, M. Shi, Q. Liu, Y.M. Lv, X.L. Chen, K.J. Zhu, Y.F. Guo, D.Y. Hu, M. Li, M. Li, Y.H. Zhang, X. Zhang, J.P. Tang, B.R. Guo, H. Wang, Y. Liu, X.Y. Zou, F.S. Zhou, X.Y. Liu, G. Chen, L. Ma, S.M. Zhang, A.P. Jiang, X.D. Zheng, X.H. Gao, P. Li, C.X. Tu, X.Y. Yin, X.P. Han, Y.Q. Ren, S.P. Song, Z.Y. Lu, X.L. Zhang, Y. Cui, J. Chang, M. Gao, X.Y. Luo, P.G. Wang, X. Dai, W. Su, H. Li, C.P. Shen, S.X. Liu, X.B. Feng, C.J. Yang, G.S. Lin, Z.X. Wang, J.Q. Huang, X. Fan, Y. Wang, Y.X. Bao, S. Yang, J.J. Liu, A. Franke, S. Weidinger, Z.R. Yao, X.J. Zhang, Nat. Genet. 43, 690 (2011)CrossRefPubMedGoogle Scholar
  26. 26.
    M. Li, R. Cheng, M. Shi, J. Liu, G. Zhang, Q. Liu, H. Yu, Z. Yao, Br. J. Dermatol. 168, 1335 (2013)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Medical MicrobiologyQingdao University Medical CollegeQingdaoChina
  2. 2.Department of Clinical LaboratoryCentral Hospital of ZiboZiboChina

Personalised recommendations