Journal of Clinical Immunology

, Volume 28, Issue 5, pp 399–404 | Cite as

Single Nucleotide Polymorphism in DNMT3B Promoter and the Risk for Idiopathic Thrombocytopenic Purpura in Chinese Population

  • Zhenping Chen
  • Zeping Zhou
  • Xiaoli Chen
  • Jianhui Xu
  • Aijuan Liu
  • Weiting Du
  • Dongsheng Gu
  • Jing Ge
  • Zhenxing Guo
  • Xiaoyan Wang
  • Xunwei Dong
  • Qian Ren
  • Renchi Yang
Article

Abstract

Objective

Epigenetic changes in gene expression, including DNA methylation and histone modifications, might contribute to autoimmunity. DNA methylation is mediated by a family of DNA methyltransferases. Polymorphisms of the DNA methyltransferase 3B (DNMT3B) gene may influence DNMT3B activity on DNA methylation, thereby modulating the susceptibility to some diseases. The purpose of this study was to investigate the association between the single nucleotide polymorphism (SNP) in promoter of the DNMT3B gene and the risk for development of idiopathic thrombocytopenic purpura (ITP).

Methods

In this hospital-based case-control study, the DNMT3B SNP was genotyped in 201 patients with ITP and 136 healthy controls by polymerase chain reaction-restriction fragment length polymorphism.

Results

The C/C genotype was not detected in both the patients with ITP and the controls. In the controls, the frequencies of T/T and C/T genotypes and T and C alleles were 97.8%, 2.2%, 98.9%, and 1.1%, respectively. There was no significant difference in genotype and allele distribution between the patients with ITP and the controls (P = 0.745 and 0.747, respectively). No significant difference was observed in genotype and allele distribution between the two groups when stratified by the age. The similar results were shown among the four groups of patients with ITP: acute childhood, chronic childhood, acute adult, and chronic adult.

Conclusion

This polymorphism was distributed similarly between the patients with ITP and the controls. It demonstrated that it may not be used as a stratification marker to predict the susceptibility to ITP, at least in the population of North China.

Keywords

DNA Methyltransferase 3B idiopathic thrombocytopenic purpura polymorphism 

Notes

Acknowledgment

This work was supported in part by grants of National Natural Science Foundation of China (30670900), Ministry of Education of China (20060023031), Ministry of Health (200802031), Ministry of Personnel of China (2006), and Tianjin Key Project for Basic Research (06YFJZJC01800).

References

  1. 1.
    Yang R, Han ZC. Pathogenesis and management of chronic idiopathic thrombocytopenic purpura: an update. Int J Hematol. 2003;71:18–24.Google Scholar
  2. 2.
    Zhou B, Zhao H, Yang RC, Han ZC. Multi-dysfunctional pathophysiology in ITP. Crit Rev Oncol Hematol. 2005;54:107–16.PubMedCrossRefGoogle Scholar
  3. 3.
    Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346:995–1008.PubMedCrossRefGoogle Scholar
  4. 4.
    Richardson B. Primer: Epigenetics of autoimmunity. Nat Clin Pract Rheumatol. 2007;3:521–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Richardson B. DNA methylation and autoimmune disease. Clin Immunol. 2003;109:72–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Robertson KD. DNA methylation and human disease. Nat Rev Genet. 2005;6:597–610.PubMedCrossRefGoogle Scholar
  7. 7.
    Sanders VM. Epigenetic regulation of Th1 and Th2 cell development. Brain Behav Immun. 2006;20:317–24.PubMedCrossRefGoogle Scholar
  8. 8.
    Sekigawa I, Okada M, Ogasawara H, Kaneko H, Hishikawa T, Hashimoto H. DNA methylation in systemic lupus erythematosus. Lupus. 2003;12:79–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Ballestar E, Esteller M, Richardson BC. The epigenetic face of systemic lupus erythematosus. J Immunol. 2006;176:7143–7.PubMedGoogle Scholar
  10. 10.
    Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet. 2000;9:2395–402.PubMedCrossRefGoogle Scholar
  11. 11.
    Robertson KD, Keyomarsi K, Gonzales FA, Velicescu M, Jones PA. Differential mrna expression of the human DNA methyltransferases (dnmts) 1, 3a and 3b during the g(0)/g(1) to s phase transition in normal and tumor cells. Nucleic Acids Res. 2000;28:2108–13.PubMedCrossRefGoogle Scholar
  12. 12.
    Liu K, Wang YF, Cantemir C, Muller MT. Endogenous assays of DNA methyltransferases: Evidence for differential activities of dnmt1, dnmt2, and dnmt3 in mammalian cells in vivo. Mol Cell Biol. 2003;23:2709–19.PubMedCrossRefGoogle Scholar
  13. 13.
    Klose RJ, Bird AP. Genomic DNA methylation: The mark and its mediators. Trends Biochem Sci. 2006;31:89–97.PubMedCrossRefGoogle Scholar
  14. 14.
    Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases dnmt3a and dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99:247–57.PubMedCrossRefGoogle Scholar
  15. 15.
    Chedin F, Lieber MR, Hsieh CL. The DNA methyltransferase-like protein dnmt3l stimulates de novo methylation by dnmt3a. Proc Natl Acad Sci U S A. 2002;99:16916–21.PubMedCrossRefGoogle Scholar
  16. 16.
    Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, et al. The dnmt3b DNA methyltransferase gene is mutated in the icf immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1999;96:14412–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Shen H, Wang L, Spitz MR, Hong WK, Mao L, Wei Q. A novel polymorphism in human cytosine DNA-methyltransferase-3b promoter is associated with an increased risk of lung cancer. Cancer Res. 2002;62:4992–5.PubMedGoogle Scholar
  18. 18.
    Wang L, Rodriguez M, Kim ES, Xu Y, Bekele N, El-Naggar AK, et al. A novel c/t polymorphism in the core promoter of human de novo cytosine DNA methyltransferase 3b6 is associated with prognosis in head and neck cancer. Int J Oncol. 2004;25:993–9.PubMedGoogle Scholar
  19. 19.
    Lee SJ, Jeon HS, Jang JS, Park SH, Lee GY, Lee BH, et al. Dnmt3b polymorphisms and risk of primary lung cancer. Carcinogenesis. 2005;26:403–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica. 2005;90:914–23.PubMedGoogle Scholar
  21. 21.
    George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, et al. Idiopathic thrombocytopenic purpura: A practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3–40.PubMedGoogle Scholar
  22. 22.
    Zeller B, Rajantie J, Hedlund-Treutiger I, Tedgard U, Wesenberg F, Jonsson OG, et al. Childhood idiopathic thrombocytopenic purpura in the nordic countries: Epidemiology and predictors of chronic disease. Acta Paediatr. 2005;94:178–84.PubMedCrossRefGoogle Scholar
  23. 23.
    Zhao H, Li H, Zhang L, Wang T, Ji L, Yang R. Retrospective analysis of 472 chinese children with chronic idiopathic thrombocytopenic purpura: A single center experience. Haematologica. 2005;90:860–1.PubMedGoogle Scholar
  24. 24.
    Chen X, Xu J, Chen Z, Zhou Z, Feng X, Zhou Y, et al. Interferon-gamma +874a/t and interleukin-4 intron3 vntr gene polymorphisms in Chinese patients with idiopathic thrombocytopenic purpura. Eur J Haematol. 2007;79:191–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Ansel KM, Lee DU, Rao A. An epigenetic view of helper T cell differentiation. Nat Immunol. 2003;4:616–23.PubMedCrossRefGoogle Scholar
  26. 26.
    Reik W, Walter J. Evolution of imprinting mechanisms: The battle of the sexes begins in the zygote. Nat Genet. 2001;27:255–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Richardson BC, Strahler JR, Pivirotto TS, Quddus J, Bayliss GE, Gross L, et al. Phenotypic and functional similarities between 5-azacytidine-treated T cells and a T cell subset in patients with active systemic lupus erythematosus. Arthritis Rheum. 1992;35:47–62.PubMedCrossRefGoogle Scholar
  28. 28.
    Narayan A, Ji W, Zhang XY, Marrogi A, Graff JR, Baylin SB, et al. Hypomethylation of pericentromeric DNA in breast adenocarcinomas. Int J Cancer. 1998;77:833–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Richardson BC, Liebling MR, Hudson JL. Cd4+ cells treated with DNA methylation inhibitors induce autologous b cell differentiation. Clin Immunol Immunopathol. 1990;55:368–81.PubMedCrossRefGoogle Scholar
  30. 30.
    Deng C, Kaplan MJ, Yang J, Ray D, Zhang Z, McCune WJ, et al. Decreased ras-mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients. Arthritis Rheum. 2001;44:397–407.PubMedCrossRefGoogle Scholar
  31. 31.
    Montgomery KG, Liu MC, Eccles DM, Campbell IG. The dnmt3b C–>T promoter polymorphism and risk of breast cancer in a British population: A case-control study. Breast Cancer Res. 2004;6:R390–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Zhenping Chen
    • 1
  • Zeping Zhou
    • 1
  • Xiaoli Chen
    • 1
  • Jianhui Xu
    • 1
  • Aijuan Liu
    • 1
  • Weiting Du
    • 1
  • Dongsheng Gu
    • 1
  • Jing Ge
    • 1
  • Zhenxing Guo
    • 1
  • Xiaoyan Wang
    • 1
  • Xunwei Dong
    • 1
  • Qian Ren
    • 1
  • Renchi Yang
    • 1
  1. 1.State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjinPeople’s Republic of China

Personalised recommendations