Methylation of class II transactivator gene promoter IV is not associated with susceptibility to Multiple Sclerosis
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- 作者：Sreeram V Ramagopalan (1) (2)
David A Dyment (1) (2)
Katie M Morrison (1) (2)
Blanca M Herrera (1) (2)
Gabriele C DeLuca (1) (2)
Matthew R Lincoln (1) (2)
Sarah M Orton (1) (2)
Lahiru Handunnetthi (1) (2)
Michael J Chao (1) (2)
A Dessa Sadovnick (3)
George C Ebers (1) (2) - 刊名：BMC Medical Genetics
- 出版年：2008
- 出版时间：December 2008
- 年：2008
- 卷：9
- 期：1
- 全文大小：786KB
- 参考文献：1. Dyment DA, Ebers GC, Sadovnick AD: Genetics of multiple sclerosis. / Lancet Neurol 2004,3(2):104鈥?10. CrossRef
2. Zhang Z, Duvefelt K, Svensson F, Masterman T, Jonasdottir G, Salter H, Emahazion T, Hellgren D, Falk G, Olsson T, Hillert J, Anvret M: Two genes encoding immune-regulatory molecules (LAG3 and IL7R) confer susceptibility to multiple sclerosis. / Genes Immun 2005,6(2):145鈥?52. CrossRef
3. Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, de Bakker PI, Gabriel SB, Mirel DB, Ivinson AJ, Pericak-Vance MA, Gregory SG, Rioux JD, McCauley JL, Haines JL, Barcellos LF, Cree B, Oksenberg JR, Hauser SL: Risk alleles for multiple sclerosis identified by a genomewide study. / N Engl J Med 2007,357(9):851鈥?62. CrossRef
4. Peltonen L: Old Suspects Found Guilty -- The First Genome Profile of Multiple Sclerosis. / N Engl J Med 2007.
5. Fogdell A, Hillert J, Sachs C, Olerup O: The multiple sclerosis- and narcolepsy-associated HLA class II haplotype includes the DRB5*0101 allele. / Tissue Antigens 1995,46(4):333鈥?36. CrossRef
6. Lincoln MR, Montpetit A, Cader MZ, Saarela J, Dyment DA, Tiislar M, Ferretti V, Tienari PJ, Sadovnick AD, Peltonen L, Ebers GC, Hudson TJ: A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. / Nat Genet 2005,37(10):1108鈥?112. CrossRef
7. Chao MJ, Barnardo MC, Bu GZ, Lincoln MR, Ramagopalan SV, Herrera BM, Dyment DA, Sadovnick AD, Ebers GC: Transmission of class I/II multi-locus MHC haplotypes and multiple sclerosis susceptibility: accounting for linkage disequilibrium. / Hum Mol Genet 2007.
8. Dyment DA, Herrera BM, Cader MZ, Willer CJ, Lincoln MR, Sadovnick AD, Risch N, Ebers GC: Complex interactions among MHC haplotypes in multiple sclerosis: susceptibility and resistance. / Hum Mol Genet 2005,14(14):2019鈥?026. CrossRef
9. Ramagopalan SV, Morris AP, Dyment DA, Herrera BM, Deluca GC, Lincoln MR, Orton SM, Chao MJ, Sadovnick AD, Ebers GC: The Inheritance of Resistance Alleles in Multiple Sclerosis. / PLoS Genet 2007,3(9):e150. CrossRef
10. Ting JP, Trowsdale J: Genetic control of MHC class II expression. / Cell 2002, 109 Suppl:S21鈥?3. CrossRef
11. Reith W, LeibundGut-Landmann S, Waldburger JM: Regulation of MHC class II gene expression by the class II transactivator. / Nat Rev Immunol 2005,5(10):793鈥?06. CrossRef
12. Morris AC, Spangler WE, Boss JM: Methylation of class II trans-activator promoter IV: a novel mechanism of MHC class II gene control. / J Immunol 2000,164(8):4143鈥?149.
13. Swanberg M, Lidman O, Padyukov L, Eriksson P, Akesson E, Jagodic M, Lobell A, Khademi M, Borjesson O, Lindgren CM, Lundman P, Brookes AJ, Kere J, Luthman H, Alfredsson L, Hillert J, Klareskog L, Hamsten A, Piehl F, Olsson T: MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction. / Nat Genet 2005,37(5):486鈥?94. CrossRef
14. Akkad DA, Jagiello P, Szyld P, Goedde R, Wieczorek S, Gross WL, Epplen JT: Promoter polymorphism rs3087456 in the MHC class II transactivator gene is not associated with susceptibility for selected autoimmune diseases in German patient groups. / Int J Immunogenet 2006,33(1):59鈥?1. CrossRef
15. Sadovnick AD, Risch NJ, Ebers GC: Canadian collaborative project on genetic susceptibility to MS, phase 2: rationale and method. Canadian Collaborative Study Group. / Can J Neurol Sci 1998,25(3):216鈥?21.
16. Ramagopalan SV, Dyment DA, Valdar W, Herrera BM, Criscuoli M, Yee IM, Sadovnick AD, Ebers GC: Autoimmune disease in families with multiple sclerosis: a population-based study. / Lancet Neurol 2007,6(7):604鈥?10. CrossRef
17. Bock C, Walter J, Paulsen M, Lengauer T: CpG island mapping by epigenome prediction. / PLoS Comput Biol 2007,3(6):e110. CrossRef
18. Sambrook J, Russell DW: Molecular cloning : a laboratory manual. / 3rd Edition Cold Spring Harbor, New York , Cold Spring Harbor Laboratory Press 2001.
19. Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. / Proc Natl Acad Sci U S A 1996,93(18):9821鈥?826. CrossRef
20. Bird AP: CpG-rich islands and the function of DNA methylation. / Nature 1986,321(6067):209鈥?13. CrossRef
21. Willer CJ, Dyment DA, Risch NJ, Sadovnick AD, Ebers GC: Twin concordance and sibling recurrence rates in multiple sclerosis. / Proc Natl Acad Sci U S A 2003,100(22):12877鈥?2882. CrossRef
22. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M: Epigenetic differences arise during the lifetime of monozygotic twins. / Proc Natl Acad Sci U S A 2005,102(30):10604鈥?0609. CrossRef
23. Willer CJ, Dyment DA, Sadovnick AD, Rothwell PM, Murray TJ, Ebers GC: Timing of birth and risk of multiple sclerosis: population based study. / Bmj 2005,330(7483):120. CrossRef
24. Dean G, Elian M: Age at immigration to England of Asian and Caribbean immigrants and the risk of developing multiple sclerosis. / J Neurol Neurosurg Psychiatry 1997,63(5):565鈥?68. CrossRef
25. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/9/63/prepub - 作者单位：Sreeram V Ramagopalan (1) (2)
David A Dyment (1) (2)
Katie M Morrison (1) (2)
Blanca M Herrera (1) (2)
Gabriele C DeLuca (1) (2)
Matthew R Lincoln (1) (2)
Sarah M Orton (1) (2)
Lahiru Handunnetthi (1) (2)
Michael J Chao (1) (2)
A Dessa Sadovnick (3)
George C Ebers (1) (2)
1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK
2. Department of Clinical Neurology, University of Oxford, Level 3, The West Wing, The John Radcliffe Hospital, Oxford, OX3 9DU, UK
3. Department of Medical Genetics and Faculty of Medicine, Division of Neurology, University of British Columbia, G920, Detwiller Pavilion, VCHA 鈥?UBC Hospital, 2211 Wesbrook Mall, Vancouver, V6T 2B5, British Columbia Canada - ISSN：1471-2350
文摘
Background Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA) is the master controller of expression of class II genes, and methylation of the promoter of this gene has been previously been shown to alter its function. In this study we sought to assess whether or not methylation of the MHC2TA promoter pIV could contribute to MS disease aetiology. Methods In DNA from peripheral blood mononuclear cells from a sample of 50 monozygotic disease discordant MS twins the MHC2TA promoter IV was sequenced and analysed by methylation specific PCR. Results No methylation or sequence variation of the MHC2TA promoter pIV was found. Conclusion The results of this study cannot support the notion that methylation of the pIV promoter of MHC2TA contributes to MS disease risk, although tissue and timing specific epigenetic modifications cannot be ruled out.