The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Replication of the results of genome-wide and candidate gene association studies on telomere length in a Korean population

  • Do, Sook Kyung (Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine) ;
  • Yoo, Seung Soo (Department of Internal Medicine, Kyungpook National University School of Medicine) ;
  • Choi, Yi Young (Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine) ;
  • Choi, Jin Eun (Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine) ;
  • Jeon, Hyo-Sung (Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine) ;
  • Lee, Won Kee (Department of Preventive Medicine, Kyungpook National University School of Medicine) ;
  • Lee, Shin Yup (Department of Internal Medicine, Kyungpook National University School of Medicine) ;
  • Lee, Jaehee (Department of Internal Medicine, Kyungpook National University School of Medicine) ;
  • Cha, Seung Ick (Department of Internal Medicine, Kyungpook National University School of Medicine) ;
  • Kim, Chang Ho (Department of Internal Medicine, Kyungpook National University School of Medicine) ;
  • Park, Jae Yong (Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine)
  • Received : 2014.04.18
  • Accepted : 2014.12.02
  • Published : 2015.09.01
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Abstract

Background/Aims: A number of genome-wide and candidate gene association studies have identified polymorphisms associated with telomere length in Caucasian populations. This study was conducted to determine the impacts of 17 polymorphisms identified in Caucasians on telomere length in a Korean population. Methods: Ninety-four healthy individuals were enrolled in this study. Relative telomere length of chromosomes from peripheral blood samples was measured using quantitative polymerase chain reaction. Results: Two polymorphisms, rs10936599 of MYNN and rs412658 of ZNF676, were found to be associated with telomere length (under dominant model, p = 0.04; under recessive model, p = 0.001). Three polymorphisms, rs2853669, rs7705526, and rs2736108, at the TERT locus were also associated with telomere length (under recessive model, p = 0.01, p = 0.02, and p = 0.01, respectively). The genotypes of the five polymorphisms associated with short telomere length were considered bad genotypes; telomere length was significantly decreased with increasing number of bad genotypes ($p=1.7{\times}10^{-5}$). Conclusions: We have identified polymorphisms associated with telomere length in a Korean population.

Keywords

Acknowledgement

Supported by : Ministry of Health and Welfare

References

  1. Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 2005;6:611-622. https://doi.org/10.1038/nrg1656
  2. Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB. Telomere end-replication problem and cell aging. J Mol Biol 1992;225:951-960. https://doi.org/10.1016/0022-2836(92)90096-3
  3. Allsopp RC, Chang E, Kashefi-Aazam M, et al. Telomere shortening is associated with cell division in vitro and in vivo. Exp Cell Res 1995;220:194-200. https://doi.org/10.1006/excr.1995.1306
  4. Blackburn EH. Structure and function of telomeres. Nature 1991;350:569-573. https://doi.org/10.1038/350569a0
  5. Aubert G, Lansdorp PM. Telomeres and aging. Physiol Rev 2008;88:557-579. https://doi.org/10.1152/physrev.00026.2007
  6. Brouilette SW, Moore JS, McMahon AD, et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet 2007;369:107-114. https://doi.org/10.1016/S0140-6736(07)60071-3
  7. Willeit P, Willeit J, Mayr A, et al. Telomere length and risk of incident cancer and cancer mortality. JAMA 2010;304:69-75. https://doi.org/10.1001/jama.2010.897
  8. Cohen SB, Graham ME, Lovrecz GO, Bache N, Robinson PJ, Reddel RR. Protein composition of catalytically active human telomerase from immortal cells. Science 2007;315:1850-1853. https://doi.org/10.1126/science.1138596
  9. Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994;266:2011-2015. https://doi.org/10.1126/science.7605428
  10. Chung IK, Hwang KY, Kim IH, et al. Helicobacter pylori and telomerase activity in intestinal metaplasia of the stomach. Korean J Intern Med 2002;17:227-233. https://doi.org/10.3904/kjim.2002.17.4.227
  11. Hsu CP, Hsu NY, Lee LW, Ko JL. Ets2 binding site single nucleotide polymorphism at the hTERT gene promoter: effect on telomerase expression and telomere length maintenance in non-small cell lung cancer. Eur J Cancer 2006;42:1466-1474. https://doi.org/10.1016/j.ejca.2006.02.014
  12. Mangino M, Richards JB, Soranzo N, et al. A genome-wide association study identifies a novel locus on chromosome 18q12.2 influencing white cell telomere length. J Med Genet 2009;46:451-454. https://doi.org/10.1136/jmg.2008.064956
  13. Levy D, Neuhausen SL, Hunt SC, et al. Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proc Natl Acad Sci U S A 2010;107:9293-9298. https://doi.org/10.1073/pnas.0911494107
  14. Prescott J, Kraft P, Chasman DI, et al. Genome-wide association study of relative telomere length. PLoS One 2011;6:e19635. https://doi.org/10.1371/journal.pone.0019635
  15. Mangino M, Hwang SJ, Spector TD, et al. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Hum Mol Genet 2012;21:5385-5394. https://doi.org/10.1093/hmg/dds382
  16. Codd V, Mangino M, van der Harst P, et al. Common variants near TERC are associated with mean telomere length. Nat Genet 2010;42:197-199. https://doi.org/10.1038/ng.532
  17. Kote-Jarai Z, Saunders EJ, Leongamornlert DA, et al. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. Hum Mol Genet 2013;22:2520-2528. https://doi.org/10.1093/hmg/ddt086
  18. Bojesen SE, Pooley KA, Johnatty SE, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet 2013;45:371-384. https://doi.org/10.1038/ng.2566
  19. Jones AM, Beggs AD, Carvajal-Carmona L, et al. TERC polymorphisms are associated both with susceptibility to colorectal cancer and with longer telomeres. Gut 2012;61:248-254. https://doi.org/10.1136/gut.2011.239772
  20. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res 2002;30:e47. https://doi.org/10.1093/nar/30.10.e47
  21. Jeon HS, Choi YY, Choi JE, et al. Telomere length of tumor tissues and survival in patients with early stage nonsmall cell lung cancer. Mol Carcinog 2014;53:272-279. https://doi.org/10.1002/mc.21972
  22. Gabriel SB, Schaffner SF, Nguyen H, et al. The structure of haplotype blocks in the human genome. Science 2002;296:2225-2229. https://doi.org/10.1126/science.1069424
  23. Alliel PM, Seddiqi N, Goudou D, et al. Myoneurin, a novel member of the BTB/POZ-zinc finger family highly expressed in human muscle. Biochem Biophys Res Commun 2000;273:385-391. https://doi.org/10.1006/bbrc.2000.2862
  24. Cifuentes-Diaz C, Bitoun M, Goudou D, et al. Neuromuscular expression of the BTB/POZ and zinc finger protein myoneurin. Muscle Nerve 2004;29:59-65. https://doi.org/10.1002/mus.10526
  25. Codd V, Nelson CP, Albrecht E, et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet 2013;45:422-427. https://doi.org/10.1038/ng.2528
  26. Pooley KA, Bojesen SE, Weischer M, et al. A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk. Hum Mol Genet 2013;22:5056-5064. https://doi.org/10.1093/hmg/ddt355
  27. Laity JH, Lee BM, Wright PE. Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 2001;11:39-46. https://doi.org/10.1016/S0959-440X(00)00167-6
  28. Isalan M, Patel SD, Balasubramanian S, Choo Y. Selection of zinc fingers that bind single-stranded telomeric DNA in the G-quadruplex conformation. Biochemistry 2001;40:830-836. https://doi.org/10.1021/bi001728v
  29. Patel SD, Isalan M, Gavory G, Ladame S, Choo Y, Balasubramanian S. Inhibition of human telomerase activity by an engineered zinc finger protein that binds G-quadruplexes. Biochemistry 2004;43:13452-13458. https://doi.org/10.1021/bi048892t
  30. Alter BP, Rosenberg PS, Giri N, Baerlocher GM, Lansdorp PM, Savage SA. Telomere length is associated with disease severity and declines with age in dyskeratosis congenita. Haematologica 2012;97:353-359. https://doi.org/10.3324/haematol.2011.055269
  31. Beesley J, Pickett HA, Johnatty SE, et al. Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers. PLoS One 2011;6:e24987. https://doi.org/10.1371/journal.pone.0024987
  32. Ranade K, Hsuing AC, Wu KD, et al. Lack of evidence for an association between alpha-adducin and blood pressure regulation in Asian populations. Am J Hypertens 2000;13(6 Pt 1):704-709. https://doi.org/10.1016/S0895-7061(00)00238-7
  33. Kao WT, Wang Y, Kleinman JE, et al. Common genetic variation in neuregulin 3 (NRG3) influences risk for schizophrenia and impacts NRG3 expression in human brain. Proc Natl Acad Sci U S A 2010;107:15619-15624. https://doi.org/10.1073/pnas.1005410107
  34. Chakkera HA, Hanson RL, Kobes S, et al. Association of variants in the carnosine peptidase 1 gene (CNDP1) with diabetic nephropathy in American Indians. Mol Genet Metab 2011;103:185-190. https://doi.org/10.1016/j.ymgme.2011.02.010
  35. Romano GH, Harari Y, Yehuda T, et al. Environmental stresses disrupt telomere length homeostasis. PLoS Genet 2013;9:e1003721. https://doi.org/10.1371/journal.pgen.1003721
  36. Greene CS, Penrod NM, Williams SM, Moore JH. Failure to replicate a genetic association may provide important clues about genetic architecture. PLoS One 2009;4:e5639. https://doi.org/10.1371/journal.pone.0005639

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