Skip to main content
SpringerLink
Log in

No association between identified multiple sclerosis non-MHC risk loci and neuromyelitis optica

  • Brief Communication
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are both autoimmune inflammatory and demyelinating disorders of the central nervous system. Recently, more than 50 MS-susceptibility single-nucleotide polymorphisms (SNPs) have been detected outside the major histocompatibility complex (MHC) region. In this study, we aimed to evaluate the association of these identified non-MHC MS risk loci with Chinese patients with NMO. Thirty-five non-MHC SNPs were selected and genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 110 NMO patients and 332 controls from southeastern China. Among the 35 SNPs, only one, rs1800693 in the TNFRSF1A locus, was nominally associated with NMO (P = 0.045, OR = 1.550, 95% CI = 1.007–2.384). However, none of the 35 SNPs was associated with NMO after Bonferroni correction. Our results showed no association between these identified non-MHC MS risk loci and NMO, suggesting there are genetic differences in the etiology of NMO and MS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004, 364: 2106–2112.

    Article  CAS  PubMed  Google Scholar 

  2. Cabrera-Gomez JA, Kurtzke JF, Gonzalez-Quevedo A, Lara-Rodriguez R. An epidemiological study of neuromyelitis optica in Cuba. J Neurol 2009, 256: 35–44.

    Article  PubMed  Google Scholar 

  3. Cabre P. Environmental changes and epidemiology of multiple sclerosis in the French West Indies. J Neurol Sci 2009, 286: 58–61.

    Article  PubMed  Google Scholar 

  4. Asgari N, Lillevang ST, Skejoe HP, Falah M, Stenager E, Kyvik KO. A population-based study of neuromyelitis optica in Caucasians. Neurology 2011, 76: 1589–1595.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007, 357: 851–862.

    Article  CAS  PubMed  Google Scholar 

  6. Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 2007, 39: 1329–1337.

    Article  CAS  PubMed  Google Scholar 

  7. Aulchenko YS, Hoppenbrouwers IA, Ramagopalan SV, Broer L, Jafari N, Hillert J, et al. Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nat Genet 2008, 40: 1402–1403.

    Article  CAS  PubMed  Google Scholar 

  8. Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene). Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet 2009, 41: 824–828.

    Article  Google Scholar 

  9. De Jager PL, Jia X, Wang J, de Bakker PI, Ottoboni L, Aggarwal NT, et al. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 2009, 41: 776–782.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Jakkula E, Leppa V, Sulonen AM, Varilo T, Kallio S, Kemppinen A, et al. Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene. Am J Hum Genet 2010, 86: 285–291.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Sanna S, Pitzalis M, Zoledziewska M, Zara I, Sidore C, Murru R, et al. Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis. Nat Genet 2010, 42: 495–497.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011, 476: 214–219.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Yamakawa K, Kuroda H, Fujihara K, Sato S, Nakashima I, Takeda A, et al. Familial neuromyelitis optica (Devic’s syndrome) with late onset in Japan. Neurology 2000, 55: 318–320.

    Article  CAS  PubMed  Google Scholar 

  14. Matiello M, Kim HJ, Kim W, Brum DG, Barreira AA, Kingsbury DJ, et al. Familial neuromyelitis optica. Neurology 2010, 75: 310–315.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006, 66: 1485–1489.

    Article  CAS  PubMed  Google Scholar 

  16. Zhao GX, Liu Y, Li ZX, Lv CZ, Traboulsee A, Sadovnick AD, et al. Variants in promoter region of CYP7A1 are associated with neuromyelitis optica but not with multiple sclerosis in the Chinese Han population. Neurosci Bull 2013, 29: 525–530

    Article  CAS  PubMed  Google Scholar 

  17. Matsuoka T, Matsushita T, Kawano Y, Osoegawa M, Ochi H, Ishizu T, et al. Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple sclerosis in Japanese. Brain 2007, 130: 1206–1223.

    Article  PubMed  Google Scholar 

  18. Buetow KH, Edmonson M, MacDonald R, Clifford R, Yip P, Kelley J, et al. High-throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Natl Acad Sci U S A 2001, 98: 581–584.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Oksenberg JR, Barcellos LF, Cree BA, Baranzini SE, Bugawan TL, Khan O, et al. Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans. Am J Hum Genet 2004, 74: 160–167.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Brum DG, Barreira AA, Louzada-Junior P, Mendes-Junior CT, Donadi EA. Association of the HLA-DRB1*15 allele group and the DRB1*1501 and DRB1*1503 alleles with multiple sclerosis in White and Mulatto samples from Brazil. J Neuroimmunol 2007, 189: 118–124.

    Article  CAS  PubMed  Google Scholar 

  21. Masterman T, Ligers A, Olsson T, Andersson M, Olerup O, Hillert J. HLA-DR15 is associated with lower age at onset in multiple sclerosis. Ann Neurol 2000, 48: 211–219.

    Article  CAS  PubMed  Google Scholar 

  22. Yamasaki K, Horiuchi I, Minohara M, Kawano Y, Ohyagi Y, Yamada T, et al. HLA-DPB1*0501 associated optico-spinal multiple sclerosis: clinical, neuroimaging and immunogenetic studies. Brain 1999, 122: 1689–1696.

    Article  PubMed  Google Scholar 

  23. Matsushita T, Matsuoka T, Isobe N, Kawano Y, Minohara M, Shi N, et al. Association of the HLA-DPB1*0501 allele with anti-aquaporin-4 antibody positivity in Japanese patients with idiopathic central nervous system demyelinating disorders. Tissue Antigens 2009, 73: 171–176.

    Article  CAS  PubMed  Google Scholar 

  24. Wang H, Dai Y, Qiu W, Zhong X, Wu A, Wang Y, et al. HLA-DPB1*0501 is associated with susceptibility to antiaquaporin-4 antibodies positive neuromyelitis optica in Southern Han Chinese. J Neuroimmunol 2011, 233: 181–184.

    Article  CAS  PubMed  Google Scholar 

  25. Deschamps R, Paturel L, Jeannin S, Chausson N, Olindo S, Bera O, et al. Different HLA class II (DRB1 and DQB1) alleles determine either susceptibility or resistance to NMO and multiple sclerosis among the French Afro-Caribbean population. Mult Scler 2011, 17: 24–31.

    Article  CAS  PubMed  Google Scholar 

  26. Yoshimura S, Isobe N, Matsushita T, Yonekawa T, Masaki K, Sato S, et al. Distinct genetic and infectious profiles in Japanese neuromyelitis optica patients according to antiaquaporin 4 antibody status. J Neurol Neurosurg Psychiatry 2013, 84: 29–34.

    Article  PubMed  Google Scholar 

  27. Kim HJ, Park HY, Kim E, Lee KS, Kim KK, Choi BO, et al. Common CYP7A1 promoter polymorphism associated with risk of neuromyelitis optica. Neurobiol Dis 2010, 37: 349–355.

    Article  CAS  PubMed  Google Scholar 

  28. Asgari N, Nielsen C, Stenager E, Kyvik KO, Lillevang ST. HLA, PTPN22 and PD-1 associations as markers of autoimmunity in neuromyelitis optica. Mult Scler 2012, 18: 23–30.

    Article  CAS  PubMed  Google Scholar 

  29. Matiello M, Schaefer-Klein JL, Hebrink DD, Kingsbury DJ, Atkinson EJ, Weinshenker BG. Genetic analysis of aquaporin-4 in neuromyelitis optica. Neurology 2011, 77: 1149–1155.

    Article  CAS  PubMed  Google Scholar 

  30. Sitarz KS, Yu-Wai-Man P, Hudson G, Jacob A, Boggild M, Horvath R, et al. Genetic variations within the OPA1 gene are not associated with neuromyelitis optica. Mult Scler 2012, 18: 240–243.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, 200040, China

    Qi-Bing Liu, Zhen-Xin Li, Gui-Xian Zhao, Hai Yu & Zhi-Ying Wu

  2. Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China

    Qi-Bing Liu

Authors
  1. Qi-Bing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhen-Xin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gui-Xian Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hai Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhi-Ying Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhi-Ying Wu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, QB., Li, ZX., Zhao, GX. et al. No association between identified multiple sclerosis non-MHC risk loci and neuromyelitis optica. Neurosci. Bull. 30, 1036–1044 (2014). https://doi.org/10.1007/s12264-013-1457-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-013-1457-1

Keywords

Search

Navigation