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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Putative association of DNA methyltransferase 1 (DNMT1) polymorphisms with clearance of HBV infection

  • Chun, Ji-Yong (Department of Life Science, Sogang University) ;
  • Bae, Joon-Seol (Department of Life Science, Sogang University) ;
  • Park, Tae-June (Department of Life Science, Sogang University) ;
  • Kim, Jason-Y. (Department of Life Science, Sogang University) ;
  • Park, Byung-Lae (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Cheong, Hyun-Sub (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Lee, Hyo-Suk (Department of Internal Medicine and Liver Research Institute, Seoul National University) ;
  • Kim, Yoon-Jun (Department of Internal Medicine and Liver Research Institute, Seoul National University) ;
  • Shin, Hyoung-Doo (Department of Life Science, Sogang University)
  • Published : 2009.12.31
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Abstract

DNA methyltransferase (DNMT) 1 is the key enzyme responsible for DNA methylation, which often occurs in CpG islands located near the regulatory regions of genes and affects transcription of specific genes. In this study, we examined the possible association of DNMT1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Seven common polymorphic sites were selected by considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n = 1,100). Statistical analysis demonstrated that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, showed significant association with HBV clearance in a co-dominant model (OR = 1.30, $P^{corr}$ = 0.03) and co- dominant/recessive model (OR = 1.34-1.74, $P^{corr}$ = 0.01-0.03), respectively. These results suggest that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, might affect HBV clearance.

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References

  1. Purcell, R. H. (1993) The discovery of the hepatitis viruses. Gastroenterology 104, 955-963 https://doi.org/10.1016/0016-5085(93)90261-A
  2. Lok, A. S., Heathcote, E. J. and Hoofnagle, J. H. (2001) Management of hepatitis B: 2000--summary of a workshop. Gastroenterology 120, 1828-1853 https://doi.org/10.1053/gast.2001.24839
  3. Thursz, M. (2001) Genetic susceptibility in chronic viral hepatitis. Antiviral. Res. 52, 113-116 https://doi.org/10.1016/S0166-3542(01)00175-9
  4. Gama-Sosa, M. A., Slagel, V. A., Trewyn, R. W., Oxenhandler, R., Kuo, K. C., Gehrke, C. W. and Ehrlich, M. (1983) The 5-methylcytosine content of DNA from human tumors. Nucleic. Acids. Res. 11, 6883-6894 https://doi.org/10.1093/nar/11.19.6883
  5. Vachtenheim, J., Horakova, I. and Novotna, H. (1994) Hypomethylation of CCGG sites in the 3' region of H-ras protooncogene is frequent and is associated with H-ras allele loss in non-small cell lung cancer. Cancer Res. 54,1145-1148
  6. Yoshiura, K., Kanai, Y., Ochiai, A., Shimoyama, Y., Sugimura, T. and Hirohashi, S. (1995) Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc. Natl. Acad. Sci. U.S.A. 92, 7416-7419 https://doi.org/10.1073/pnas.92.16.7416
  7. Eguchi, K., Kanai, Y., Kobayashi, K. and Hirohashi, S. (1997) DNA hypermethylation at the D17S5 locus in non-small cell lung cancers: its association with smoking history. Cancer Res. 57, 4913-4915
  8. Kanai, Y., Ushijima, S., Ochiai, A., Eguchi, K., Hui, A. and Hirohashi, S. (1998) DNA hypermethylation at the D17S5 locus is associated with gastric carcinogenesis. Cancer Lett. 122, 135-141 https://doi.org/10.1016/S0304-3835(97)00380-7
  9. Shen, J. C., Rideout, W. M., 3rd and Jones, P. A. (1992) High frequency mutagenesis by a DNA methyltransferase. Cell 71, 1073-1080 https://doi.org/10.1016/S0092-8674(05)80057-1
  10. Makos, M., Nelkin, B. D., Reiter, R. E., Gnarra, J. R., Brooks, J., Isaacs, W., Linehan, M. and Baylin, S. B. (1993) Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors. Cancer Res. 53, 2719-2722
  11. Chen, R. Z., Pettersson, U., Beard, C., Jackson-Grusby, L. and Jaenisch, R. (1998) DNA hypomethylation leads to elevated mutation rates. Nature 395, 89-93 https://doi.org/10.1038/25779
  12. Baylin, S. B., Esteller, M., Rountree, M. R., Bachman, K. E., Schuebel, K. and Herman, J. G. (2001) Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum. Mol. Genet. 10, 687-692 https://doi.org/10.1093/hmg/10.7.687
  13. Jones, P. A. and Baylin, S. B. (2002) The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3, 415-428
  14. Robertson, K. D. (2002) DNA methylation and chromatin - unraveling the tangled web. Oncogene 21, 5361-5379 https://doi.org/10.1038/sj.onc.1205609
  15. Robertson, K. D. (2001) DNA methylation, methyltransferases, and cancer. Oncogene 20, 3139-3155 https://doi.org/10.1038/sj.onc.1204341
  16. Garinis, G. A., Patrinos, G. P., Spanakis, N. E. and Menounos, P. G. (2002) DNA hypermethylation: when tumour suppressor genes go silent. Hum. Genet. 111, 115-127 https://doi.org/10.1007/s00439-002-0783-6
  17. Nephew, K. P. and Huang, T. H. (2003) Epigenetic gene silencing in cancer initiation and progression. Cancer Lett. 190, 125-133 https://doi.org/10.1016/S0304-3835(02)00511-6
  18. Lee, S., Lee, H. J., Kim, J. H., Lee, H. S., Jang, J. J. and Kang, G. H. (2003) Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis. Am. J. Pathol. 163, 1371-1378 https://doi.org/10.1016/S0002-9440(10)63495-5
  19. Yang, B., Guo, M., Herman, J. G. and Clark, D. P. (2003) Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma. Am. J. Pathol. 163, 1101-1107 https://doi.org/10.1016/S0002-9440(10)63469-4
  20. Saito, Y., Kanai, Y., Sakamoto, M., Saito, H., Ishii, H. and Hirohashi, S. (2001) Expression of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and DNA methylation status on CpG islands and pericentromeric satellite regions during human hepatocarcinogenesis. Hepatology 33, 561-568 https://doi.org/10.1053/jhep.2001.22507
  21. Kondo, Y., Kanai, Y., Sakamoto, M., Mizokami, M., Ueda, R. and Hirohashi, S. (2000) Genetic instability and aberrant DNA methylation in chronic hepatitis and cirrhosis--A comprehensive study of loss of heterozygosity and microsatelliteinstability at 39 loci and DNA hypermethylation on 8 CpG islands in microdissected specimens from patients with hepatocellular carcinoma. Hepatology 32, 970-979 https://doi.org/10.1053/jhep.2000.19797
  22. Ishiguro, A., Takahata, T., Saito, M., Yoshiya, G., Tamura, Y., Sasaki, M. and Munakata, A. (2006) Influence of methylated p15 and p16 genes on clinicopathological features in colorectal cancer. J. Gastroenterol. Hepatol. 21,1334-1339 https://doi.org/10.1111/j.1440-1746.2006.04137.x
  23. Roncalli, M., Bianchi, P., Bruni, B., Laghi, L., Destro, A., Di Gioia, S., Gennari, L., Tommasini, M., Malesci, A. and Coggi, G. (2002) Methylation framework of cell cycle gene inhibitors in cirrhosis and associated hepatocellular carcinoma. Hepatology 36, 427-432 https://doi.org/10.1053/jhep.2002.34852
  24. Bestor, T., Laudano, A., Mattaliano, R. and Ingram, V. (1988) Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J. Mol. Biol. 203, 971-983 https://doi.org/10.1016/0022-2836(88)90122-2
  25. Okano, M., Xie, S. and Li, E. (1998) Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat. Genet. 19, 219-220 https://doi.org/10.1038/890
  26. Jung, J. K., Arora, P., Pagano, J. S. and Jang, K. L. (2007) Expression of DNA methyltransferase 1 is activated by hepatitis B virus X protein via a regulatory circuit involving the p16INK4a-cyclin D1-CDK 4/6-pRb-E2F1 pathway. Cancer Res. 67, 5771-5778 https://doi.org/10.1158/0008-5472.CAN-07-0529
  27. Liu, X., Xu, Q., Chen, W., Cao, H., Zheng, R. and Li, G. (2009) Hepatitis B virus DNA-induced carcinogenesis of human normal liver cells by virtue of nonmethylated CpG DNA. Oncol. Rep. 21, 941-947
  28. Chen, T. and Li, E. (2004) Structure and function of eukaryotic DNA methyltransferases. Curr. Top. Dev. Biol. 60, 55-89 https://doi.org/10.1016/S0070-2153(04)60003-2
  29. Oh, B. K., Kim, H., Park, H. J., Shim, Y. H., Choi, J., Park, C. and Park, Y. N. (2007) DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation. Int. J. Mol. Med. 20, 65-73
  30. Lin, C. H., Hsieh, S. Y., Sheen, I. S., Lee, W. C., Chen, T. C., Shyu, W. C. and Liaw, Y. F. (2001) Genome-wide hypomethylation in hepatocellular carcinogenesis. Cancer Res. 61, 4238-4243
  31. Bestor, T. H. (1992) Activation of mammalian DNA methyltransferase by cleavage of a Zn binding regulatory domain. Embo. J. 11, 2611-2617
  32. Chuang, L. S., Ian, H. I., Koh, T. W., Ng, H. H., Xu, G. and Li, B. F. (1997) Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 277, 1996-2000 https://doi.org/10.1126/science.277.5334.1996
  33. Saito, Y., Kanai, Y., Nakagawa, T., Sakamoto, M., Saito, H., Ishii, H. and Hirohashi, S. (2003) Increased protein expression of DNA methyltransferase (DNMT) 1 is significantly correlated with the malignant potential and poorprognosis of human hepatocellular carcinomas. Int. J. Cancer 105, 527-532 https://doi.org/10.1002/ijc.11127
  34. Bruix, J., Sherman, M., Llovet, J. M., Beaugrand, M., Lencioni, R., Burroughs, A. K., Christensen, E., Pagliaro, L., Colombo, M. and Rodes, J. (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J. Hepatol. 35, 421-430 https://doi.org/10.1016/S0168-8278(01)00130-1
  35. Livak, K. J. (1999) Allelic discrimination using fluorogenic probes and the 5' nuclease assay. Genet. Anal. 14, 143-149 https://doi.org/10.1016/S1050-3862(98)00019-9
  36. Hedrick, P. and Kumar, S. (2001) Mutation and linkage disequilibrium in human mtDNA. Eur. J. Hum. Genet. 9, 969-972 https://doi.org/10.1038/sj.ejhg.5200735
  37. Barrett, J. C., Fry, B., Maller, J. and Daly, M. J. (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263-265 https://doi.org/10.1093/bioinformatics/bth457
  38. Stephens, M., Smith, N. J. and Donnelly, P. (2001) A newstatistical method for haplotype reconstruction from populationdata. Am. J. Hum. Genet. 68, 978-989 https://doi.org/10.1086/319501
  39. Bae, S. H., Yoon, S. K., Jang, J. W., Kim, C. W., Nam, S. W., Choi, J. Y., Kim, B. S., Park, Y. M., Suzuki, S., Sugauchi, F. and Mizokami, M. (2005) Hepatitis B virus genotype C prevails among chronic carriers of the virus in Korea. J. Korean Med. Sci. 20, 816-820 https://doi.org/10.3346/jkms.2005.20.5.816
  40. Odgerel, Z., Nho, K. B., Moon, J. Y., Kee, S. H., Park, K. S., Song, K. J., Baek, L. J., Yeon, J. E., Byun, K. S., Lee, C. H. and Song, J. W. (2003) Complete genome sequence and phylogenetic analysis of hepatitis B virus (HBV) isolatesfrom patients with chronic HBV infection in Korea. J. Med. Virol. 71, 499-503 https://doi.org/10.1002/jmv.10506
  41. Song, B. C., Cui, X. J. and Kim, H. (2005) Hepatitis B virus genotypes in Korea: an endemic area of hepatitis B virus infection. Intervirology 48, 133-137 https://doi.org/10.1159/000081740
  42. Song, B. C., Kim, H., Kim, S. H., Cha, C. Y., Kook, Y. H. and Kim, B. J. (2005) Comparison of full length sequences of hepatitis B virus isolates in hepatocellular carcinoma patients and asymptomatic carriers of Korea. J. Med. Virol. 75, 13-19 https://doi.org/10.1002/jmv.20230
  43. Yoo, B. C., Park, J. W., Kim, H. J., Lee, D. H., Cha, Y. J. and Park, S. M. (2003) Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen-negative chronic hepatitis B in Korea. J. Hepatol. 38, 98-103
  44. Nyholt, D. R. (2004) A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am. J. Hum. Genet. 74, 765-769 https://doi.org/10.1086/383251

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