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Genetics of multiple sclerosis today

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Abstract

Multiple sclerosis is a common multifactorial disease in which the etiology of the interaction between external factors and structural specificities of a large number of genes plays an important role. Identification of the risk factors for multiple sclerosis and the development of an integrated pathogenesis model is a challenging task for neurology. The goal of the current review is to describe current approaches to studying the genetics of multifactorial diseases on the whole and multiple sclerosis in particular. Basic approaches to the design of the genetic epidemiological studies are described. Towards this end we discuss the gene candidate and the whole-genome methods of studying genetic associations, the statistical approaches used to combine the diverse data, namely, meta-analysis of the results of different studies, analysis of the association with groups of functionally related genes, and comparison of the genetic bases of the diseases with similar pathogenesis.

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References

  • Abdeen, H., Heggarty, S., Hawkins, S.A., et al., Mapping candidate non-MHC susceptibility regions to multiple sclerosis, Genes Immun., 2006, vol. 7, no. 6, pp. 494–502. doi 10.1038/sjgene.6364320

    Article  CAS  PubMed  Google Scholar 

  • Akesson, E., Oturai, A., Berg, J., et al., A genome-wide screen for linkage in Nordic sib-pairs with multiple sclerosis, Genes Immun., 2002, vol. 3, no. 5, pp. 279–285. doi 10.1038/sjgene.6363866

    Article  CAS  PubMed  Google Scholar 

  • Al-Shammri, S., Fatania, H., Al-Radwan, R., and Akanji, A.O., The relationship of APOE genetic polymorphism with susceptibility to multiple sclerosis and its clinical phenotypes in Kuwaiti Arab subjects, Clin. Chim. Acta, 2005, vol. 351, nos. 1–4, pp. 203–207. doi 10.1016/jcccn.2004.09.015

    Article  CAS  PubMed  Google Scholar 

  • Aulchenko, Y.S., Hoppenbrouwers, I.A., Ramagopalan, S.V., et al., Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis, Nat. Genet., 2008, vol. 40, no. 12, pp. 1402–1403. doi 10.1038/ng.251

    Article  CAS  PubMed  Google Scholar 

  • Bahlo, M., Booth, D.R., Broadley, S.A., et al., Genomewide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20, Nat. Genet., 2009, vol. 41, no. 7, pp. 824–828. doi 10.1038/ng.396

    Article  CAS  Google Scholar 

  • Ban, M., Stewart, G.J., Bennetts, B.H., et al., A genome screen for linkage in Australian sibling-pairs with multiple sclerosis, Genes Immun., 2002, vol. 3, no. 8, pp. 464–469. doi 10.1038/sjgene.6363910

    Article  CAS  PubMed  Google Scholar 

  • Baranzini, S.E., The genetics of autoimmune diseases: a networked perspective, Curr. Opinion Immunol., 2009, vol. 21, no. 6, pp. 596–605. doi 10.1016/jcoi.2009. 09.014

    Article  CAS  Google Scholar 

  • Baranzini, S.E., Galwey, N.W., Wang, J., et al., Pathway and network-based analysis of genome-wide association studies in multiple sclerosis, Hum. Mol. Genet., 2009b, vol. 18, no. 11, pp. 2078–2090. doi 10.1093/hmg/ddp120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baranzini, S.E., Khankhanian, P., Patsopoulos, N.A., et al., Network-based multiple sclerosis pathway analysis with GWAS data from 15000 cases and 30000 controls, Am. J. Hum. Genet., 2013, vol. 923, no. 6, pp. 854–865. doi 10.1016/jajhg.2013.04.019

    Google Scholar 

  • Baranzini, S.E., Wang, J., Gibson, R.A., et al., Genomewide association analysis of susceptibility and clinical phenotype in multiple sclerosis, Hum. Mol. Genet., 2009a, vol. 18, no. 4, pp. 767–768. doi 10.1093/hmg/ddn388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barcellos, L.F., Thomson, G., Carrington, M., et al., Chromosome 19 single-locus and multilocus haplotype associations with multiple sclerosis. Evidence of a new susceptibility locus in Caucasian and Chinese patients, J. Am. Med. Assoc., 1997, vol. 278, no. 15, pp. 1256–1261.

    Article  CAS  Google Scholar 

  • Bettencourt, A., Martins da Silva, A., Pinho, E., Costa, P., and Martins Silva, B., Molecular genetic studies of multiple sclerosis in the Portuguese population, Acta Med. Port., 2012, vol. 25, no. 4, pp. 224–230.

    PubMed  Google Scholar 

  • Bielecki, B., Mycko, M.P., Tronczynska, E., et al., A whole genome screen for association in Polish multiple sclerosis patients, J. Neuroimmunol., 2003, vol. 143, nos. 1–4, pp. 107–111.

    Article  CAS  PubMed  Google Scholar 

  • Boiko, A.N., Smirnova, N.F., Zolotova, S.N., and Gusev, E.I., Epidemiology and etiology of disseminated sclerosis, Consilium Med., 2008, vol. 10, no. 7.

    Google Scholar 

  • Bonetti, A., Koivisto, K., Pirttila, T., et al., A follow-up study of chromosome 19q13 in multiple sclerosis susceptibility, J. Neuroimmunol., 2009, vol. 208, nos. 1–4, pp. 119–124. doi 10.1016/jjneuroim.2009.01.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Booth, D., Heard, R., Stewart, G., et al., Refining genetic associations in multiple sclerosis, Lancet Neurol., 2008, vol. 7, no. 7, pp. 567–569. doi 10.1016/S14744422(08)70122-4

    Article  Google Scholar 

  • Brahic, M., Multiple sclerosis and viruses, Ann. Neurol., 2010, vol. 68, no. 1, pp. 6–8. doi 10.1002/ana.22057

    Article  PubMed  Google Scholar 

  • Broadley, S., Sawcer, S., D’Alfonso, S., et al., A genome screen for multiple sclerosis in Italian families, Genes Immun., 2001, vol. 2, no. 4, pp. 205–210. doi 10.1038/sjgene.6363758

    Article  CAS  PubMed  Google Scholar 

  • Burton, P.R., Clayton, D.G., Cardon, L.R., et al., Association scan of 14500 nonsynonymous SNPs in four diseases identifies autoimmunity variants, Nat. Genet., 2007, vol. 39, no. 11, pp. 1329–1337. doi 10.1038/ng.2007.17

    Article  CAS  PubMed  Google Scholar 

  • Carlin, C., Murray, L., Graham, D., et al., Involvement of apolipoprotein E in multiple sclerosis: absence of remyelination associated with possession of the APOE epsilon2 allele, J. Neuropathol. Exp. Neurol., 2000, vol. 59, no. 5, pp. 361–367.

    Article  CAS  PubMed  Google Scholar 

  • Chapman, J., Sylantiev, C., Nisipeanu, P., and Korczyn, A.D., Preliminary observations on APOE epsilon4 allele and progression of disability in multiple sclerosis, Arch. Neurol., 1999, vol. 56, no. 12, pp. 1484–1487.

    Article  CAS  PubMed  Google Scholar 

  • Chapman, J., Vinokurov, S., Achiron, A., et al., APOE genotype is a major predictor of long-term progression of disability in MS, Neurology, 2001, vol. 56, no. 3, pp. 312–316.

    Article  CAS  PubMed  Google Scholar 

  • Chasman, D.I., Paré, G., and Ridker, P.M., Populationbased genome-wide genetic analysis of common clinical chemistry analyses, Clin. Chem., 2009, vol. 55, no. 1, pp. 39–51. doi 10.1373/clinchem.2008.107243

    Article  CAS  PubMed  Google Scholar 

  • Comabella, M., Craig, D.W., Camiña-Tato, M., et al., Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500000 single nucleotide polymorphisms, PLoS One, 2008, vol. 3, no. 10. p. e3490. doi 10.1371/journalpone. 0003490

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Compston, A., Making progress on the natural history of multiple sclerosis, J. Neurol., 2006, vol. 129, part 3, pp. 561–563. doi 10.1093/brain/awl034

    Google Scholar 

  • Coraddu, F., Lai, M., Mancosu, C., et al., A genome-wide screen for linkage disequilibrium in Sardinian multiple sclerosis, J. Neuroimmunol., 2003, vol. 143, nos. 1–4, pp. 120–123.

    Article  CAS  PubMed  Google Scholar 

  • Coraddu, F., Sawcer, S., D’Alfonso, S., et al., A genome screen for multiple sclerosis in Sardinian multiplex families, Eur. J. Hum. Genet., 2001, vol. 9, no. 8, pp. 621–626. doi 10.1038/sjejhg.5200680

    Article  CAS  PubMed  Google Scholar 

  • Corona, T., Guerrero-Camacho, J.L., Alonso-Vilatela, M.E., and Flores-Rivera, J.J., The absence of a relation between apolipoprotein E genotypes and the severity of multiple sclerosis in Mexican patients, Rev. Neurol., 2010, vol. 50, no. 1, pp. 19–22.

    PubMed  Google Scholar 

  • Curtis, R.K., Oresic, M., and Vidal-Puig, A., Pathways to the analysis of microarray data, Trends Biotechnol., 2005, vol. 23, no. 8, pp. 429–435. doi 10.1016/jtibtech.2005.05.011

    Article  CAS  PubMed  Google Scholar 

  • De Jager, P.L., Jia, X., Wang, J., et al., Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci, Nat. Genet., 2009, vol. 41, no. 7, pp. 776–782. doi 10.1038/ng.401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Stefano, N., Bartolozzi, M.L., Nacmias, B., et al., Influence of apolipoprotein E epsilon4 genotype on brain tissue integrity in relapsing-remitting multiple sclerosis, Arch. Neurol., 2004, vol. 61, no. 4, pp. 536–540. doi 10.1001/archneur.61.4.536

    Article  PubMed  Google Scholar 

  • Durant, L., Watford, W.T., Ramos, H.L., et al., Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis, Immunity, 2010, vol. 32, no. 5, pp. 605–615. doi 10.1016/jimmuni. 2010.05.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dyment, D.A., Yee, I.M.L., Ebers, G.C., and Sadovnick, A.D., Multiple sclerosis in stepsiblings: recurrence risk and ascertainment, J. Neurol., Neurosurg., Psychiatry, 2006, vol. 77, no. 2, pp. 258–259. doi 10.1136/jnnp. 2005.063008

    Article  CAS  Google Scholar 

  • Ebers, G.C., Kukay, K., Bulman, D.E., et al., A full genome search in multiple sclerosis, Nat. Genet., 1996, vol. 13, no. 4, pp. 472–476. doi 10.1038/ng0896-472

    Article  CAS  PubMed  Google Scholar 

  • Ebers, G.C., Sadovnick, A.D., and Risch, N.J., A genetic basis for familial aggregation in multiple sclerosis, Nature, 1995, vol. 377, no. 6545, pp. 150–151. doi 10.1038/377150a0

    Article  CAS  PubMed  Google Scholar 

  • Enzinger, C., Ropele, S., Strasser-Fuchs, S., et al., Lower levels of N-acetylaspartate in multiple sclerosis patients with the apolipoprotein E epsilon4 allele, Arch. Neurol., 2003, vol. 60, no. 1, pp. 65–70.

    Article  PubMed  Google Scholar 

  • Eraksoy, M., Kurtuncu, M., Akman-Demir, G., et al., A whole genome screen for linkage in Turkish multiple sclerosis, J. Neuroimmunol., 2003, vol. 143, nos. 1–4, pp. 17–24.

    Article  CAS  PubMed  Google Scholar 

  • Esposito, F., Patsopoulos, N.A., Cepok, S., et al., IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci, Genes Immun., 2010, vol. 11, no. 5, pp. 397–405. doi 10.1038/gene.2010.28

    Article  CAS  Google Scholar 

  • Evangelou, N., Jackson, M., Beeson, D., and Palace, J., Association of the APOE epsilon4 allele with disease activity in multiple sclerosis, J. Neurol., Neurosur., Psychiatry, 1999, vol. 67, no. 2, pp. 203–205.

    Article  CAS  Google Scholar 

  • Favorova, O.O., Kulakova, O.G., and Boiko, A.N., Multiple sclerosis as a polygenic disease: an update, Russ. J. Genet., 2010, vol. 46, no. 3, pp. 265–275.

    Article  CAS  Google Scholar 

  • Fazekas, F., Strasser-Fuchs, S., Kollegger, H., et al., Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis, Neurology, 2001, vol. 57, no. 5, pp. 853–857.

    Article  CAS  PubMed  Google Scholar 

  • Fazekas, F., Strasser-Fuchs, S., Schmidt, H., et al., Apolipoprotein E genotype related differences in brain lesions of multiple sclerosis, J. Neurol., Neurosurg., Psychiatry, 2000, vol. 69, no. 1, pp. 25–28.

    Article  CAS  Google Scholar 

  • Ferri, C., Sciacca, F.L., Veglia, F., et al., APOE epsilon2-4 and -491 polymorphisms are not associated with MS, Neurology, 1999, vol. 53, no. 4, pp. 888–889.

    Article  CAS  PubMed  Google Scholar 

  • Franke, L., van Bakel, H., Fokkens, L., et al., Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes, Am. J. Hum. Genet., 2006, vol. 78, no. 6, pp. 1011–1025. doi 10.1086/504300

    CAS  PubMed  Google Scholar 

  • Friedrich, C., Multiple Sklerose und Erbanlage, Leipzig: Georg Thieme, 1933, p. 226.

    Google Scholar 

  • Ghaffar, O., Reis, M., Pennell, N., et al., APOE epsilon4 and the cognitive genetics of multiple sclerosis, Neurology, 2010, vol. 74, no. 20, pp. 1611–1618. doi 10.1212/WNL.0b013e3181e074a7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glass, G.V., Mc Gaw, B., and Smith, M.L., Meta-Analysis in Social Research, Beverly Hills, CA: Sage, 1981, p. 279.

    Google Scholar 

  • Gödde, R., Nigmatova, V., Jagiello, P., et al., Refining the results of a whole-genome screen based on 4666 microsatellite markers for defining predisposition factors for multiple sclerosis, Electrophoresis, 2004, vol. 25, no. 14, pp. 2212–2218. doi 10.1002/elps.200405929

    Article  PubMed  CAS  Google Scholar 

  • Gödde, R., Rohde, K., Becker, C., et al., Association of the HLA region with multiple sclerosis as confirmed by a genome screen using 10000 SNPs on DNA chips, J. Mol. Med., 2005, vol. 83, no. 6, pp. 486–494. doi 10.1007/s00109-005-0650-8

    Article  PubMed  CAS  Google Scholar 

  • Gold, M.S. and McIntyre, P., Human papillomavirus vaccine safety in Australia: experience to date and issues for surveillance, Sex. Health, 2010, vol. 7, no. 3, pp. 320–324. doi 10.1071/SH09153

    Article  PubMed  Google Scholar 

  • Goris, A., Pauwels, I., and Dubois, B., Progress in multiple sclerosis genetics, Curr. Genome, 2012, vol. 13, no. 8, pp. 646–663. doi 10.2174/138920212803759695

    Article  CAS  Google Scholar 

  • Goris, A., Sawcer, S., Vandenbroeck, K., et al., New candidate loci for multiple sclerosis susceptibility revealed by a whole genome association screen in a Belgian population, J. Neuroimmunol., 2003, vol. 143, nos. 1–4, pp. 65–69.

    Article  CAS  PubMed  Google Scholar 

  • Guerrero, A.L., Bueno, V., Hernández, M.T., et al., Apolipoprotein E polymorphism as a predictor of progression of multiple sclerosis, Neurología, 2003, vol. 18, no. 3, pp. 146–148.

    CAS  PubMed  Google Scholar 

  • Guerrero, A.L., Laherrán, E., Gutiérrez, F., et al., Apolipoprotein E genotype does not associate with disease severity measured by Multiple Sclerosis Severity Score, Acta Neurol. Scand., 2008, vol. 117, no. 1, pp. 21–25. doi 10.1111/j.1600-0404.2007.00908x

    CAS  PubMed  Google Scholar 

  • Hafler, D.A., Compston, A., Sawcer, S., et al., Risk alleles for multiple sclerosis identified by a genomewide study, N. Engl. J. Med., 2007, vol. 357, no. 9, pp. 851–862. doi 10.1056/NEJMoa073493

    Article  CAS  PubMed  Google Scholar 

  • Haines, J.L., Ter-Minassian, M., Bazyk, A., et al., A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex, Nat. Genet., 1996, vol. 13, no. 4, pp. 469–471. doi 10.1038/ng0896–469

    Article  CAS  PubMed  Google Scholar 

  • Hensiek, A.E., Roxburgh, R., Smilie, B., et al., Updated results of the United Kingdom linkage-based genome screen in multiple sclerosis, J. Neuroimmunol., 2003, vol. 143, nos. 1–4, pp. 25–30.

    Article  CAS  PubMed  Google Scholar 

  • Hoffjan, S. and Akkad, D.A., The genetics of multiple sclerosis: an update 2010, Mol. Cell. Probes, 2010, vol. 24, no. 5, pp. 237–243. doi 10.1016/jmcp. 2010.04.006

    Article  CAS  PubMed  Google Scholar 

  • Jakkula, E., Leppä, V., Sulonen, A.M., et al., Genomewide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene, Am. J. Hum. Genet., 2010, vol. 86, no. 2, pp. 285–291. doi 10.1016/jajhg.2010.01.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jersild, C., Hansen, G., Svejgaard, A., et al., Histocompatibility detrminants in multiple sclerosis, with special reference to clinical course, Lancet, 1973, vol. 302, no. 7840, pp. 1221–1225. doi 10.1016/S0140-6736(73)90970-7

    Google Scholar 

  • Jersild, C., Svejgaard, A., and Fog, T., HL-A antigens and multiple sclerosis, Lancet, 1972, vol. 1, no. 7762, pp. 1240–1241.

    Article  CAS  PubMed  Google Scholar 

  • Julian, L.J., Vella, L., Frankel, D., et al., APOE alleles, depression, and positive affect in multiple sclerosis, Mult. Scler., 2009, vol. 15, no. 3, pp. 311–315. doi 10.1177/1352458508099478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kantarci, O.H., Hebrink, D.D., Achenbach, S.J., et al., Association of APOE polymorphisms with disease severity in MS is limited to women, Neurology, 2004, vol. 62, no. 5, pp. 811–814.

    Article  CAS  PubMed  Google Scholar 

  • Kenealy, S.J., Babron, M.C., Bradford, Y., et al., A second generation genomic screen for multiple sclerosis, Am. J. Hum. Genet., 2004, vol. 75, no. 6, pp. 1070–1078. doi 10.1086/426459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Köhler, S., Bauer, S., Horn, D., and Robinson, P.N., Walking the interactome for prioritization of candidate disease genes, Am. J. Hum. Genet., 2008, vol. 82, no. 4, pp. 949–958. doi 10.1016/jajhg.2008.02.013

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kümpfel, T., Hoffmann, L.A., Rübsamen, H., et al., Late onset tumor necrosis factor receptor-associated periodic syndrome in multiple sclerosis patients carrying the TNFRSF1A R92Q mutation, Arthritis Rheum., 2007, vol. 56, no. 8, pp. 2774–2783. doi 10.1002/art.22795

    Article  PubMed  CAS  Google Scholar 

  • Kuokkanen, S., Gschwend, M., Rioux, J.D., et al., Genomewide scan of multiple sclerosis in Finnish multiplex families, Am. J. Hum. Genet., 1997, vol. 61, no. 6, pp. 1379–1387. doi 10.1086/301637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lanzillo, R., Prinster, A., Scarano, V., et al., Neuropsychological aßsessment, quantitative MRI and APOE gene polymorphisms in a series of MS patients treated with IFNß-1b, J. Neurol. Sci., 2006, vol. 245, nos. 1–4, pp. 141–145. doi 10.1016/jjns.2005.08.023

    CAS  Google Scholar 

  • Leppä, V., Surakka, I., Tienari, P.J., et al. The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study, PLoS One, 2011, vol. 6, no. 4. p. e18813. doi 10.1371/journalpone.0018813

    Article  CAS  Google Scholar 

  • Liguori, M., Sawcer, S., Setakis, E., et al., A whole genome screen for linkage disequilibrium in multiple sclerosis performed in a continental Italian population, J. Neuroimmunol., 2003, vol. 143, nos. 1–4, pp. 97–100.

    Article  CAS  PubMed  Google Scholar 

  • Lill, C.M., Liu, T., Schjeide, B.M., et al., Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29000 subjects, J. Med. Genet., 2012, vol. 49, no. 9, pp. 558–562. doi 10.1136/jmedgenet2012-101175

    Article  CAS  PubMed  Google Scholar 

  • Losonczi, E., Bencsik, K., Fricska-Nagy, Z., et al., APOE epsilon status in Hungarian patients with primary progressive multiple sclerosis, Swiss Med. Weekly, 2010, vol. 140, p. 13119. doi 10.4414/smw.2010.13119

    Google Scholar 

  • Lünemann, J.D., Kamradt, T., Martin, R., and Münz, C., Epstein-Barr virus: environmental trigger of multiple sclerosis? J. Virol., 2007, vol. 81, no. 13, pp. 6777–6784. doi 10.1128/JVI.00153-07

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Masterman, T., Zhang, Z., Hellgren, D., et al., APOE genotypes and disease severity in multiple sclerosis, Mult. Scler., 2002, vol. 8, no. 2, pp. 98–103.

    Article  CAS  PubMed  Google Scholar 

  • McCauley, J.L., Zuvich, R.L., Beecham, A.L., et al., Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci, Hum. Mol. Genet., 2010, vol. 19, no. 5, pp. 953–962. doi 10.1093/hmg/ddp542

    Article  CAS  PubMed Central  Google Scholar 

  • McWhirter, R.E., McQuillan, R., Visser, E., et al., Genome-wide homozygosity and multiple sclerosis in Orkney and Shetland Islanders, Eur. J. Hum. Genet., 2012, vol. 20, no. 2, pp. 198–202. doi 10.1038/ejhg.2011.170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minegishi, Y., Saito, M., Tsuchiya, S., et al., Dominantnegative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome, Nature, 2007, vol. 448, no. 7157, pp. 1058–1062. doi 10.1038/nature06096

    Article  CAS  PubMed  Google Scholar 

  • Mustafina, O.E., Bakhtiiarova, K.Z., Mikha lova, A.M., et al., Analysis of the association of allelic variants of apolypoprotein E and interleukin 1 beta genes with multiple sclerosis in ethnic Tatars, Russ. J. Genet., 2008a, vol. 44, no. 3, pp. 407–413.

    Article  CAS  Google Scholar 

  • Mustafina, O.E., Mikha lova, A.M., Bakhtiiarova, K.Z., et al., Polymorphism of APOE gene and risk of development of the multiple sclerosis at ethnic Russians, Mol. Biol., 2008b, vol. 42, no. 6, pp. 957–964.

    Article  CAS  Google Scholar 

  • Natio, S., Namerow, N., Mickey, M.R., and Terasaki, P.I., Multiple sclerosis: association with HL-A3, Tissue Antigens, 2008, vol. 2, no. 1, pp. 1–4. doi 10.1111/j.1399-0039.1972tb00111x

    Article  Google Scholar 

  • Niino, M., Kikuchi, S., Fukazawa, T., et al., Polymorphisms of apolipoprotein E and Japanese patients with multiple sclerosis, Mult. Scler., 2003, vol. 9, no. 4, pp. 382–386.

    Article  CAS  PubMed  Google Scholar 

  • Nischwitz, S., Cepok, S., Kroner, A., et al., Evidence for VAV2 and ZNF433 as susceptibility genes for multiple sclerosis, J. Neuroimmunol., 2010, vol. 227, nos. 1–4, pp. 162–166. doi 10.1016/jjneuroim.2010.06.003

    Article  CAS  PubMed  Google Scholar 

  • Oliveri, R.L., Cittadella, R., Sibilia, G., et al., APOE and risk of cognitive impairment in multiple sclerosis, Acta Neurol. Scand., 1999, vol. 100, no. 5, pp. 290–295.

    Article  CAS  PubMed  Google Scholar 

  • Parmenter, B.A., Denney, D.R., Lynch, S.G., et al., Cognitive impairment in patients with multiple sclerosis: association with the APOE gene and promoter polymorphisms, Mult. Scler., 2007, vol. 13, no. 1, pp. 25–32.

    Article  CAS  PubMed  Google Scholar 

  • Pe’er, I., Yelensky, R., Altshuler, D., and Daly, M.J., Estimation of the multiple testing burden for genome wide association studies of nearly all common variants, Genet. Epidemiol., 2008, vol. 32, no. 4, pp. 381–385. doi 10.1002/gepi.20303

    Article  PubMed  Google Scholar 

  • Pirttilä, T., Haanpää, M., Mehta, P.D., and Lehtimäki, T., Apolipoprotein E (APOE) phenotype and APOE concentrations in multiple sclerosis and acute herpes zoster, Acta Neurol. Scand., 2000, vol. 102, no. 2, pp. 94–98.

    Article  PubMed  Google Scholar 

  • Portaccio, E., Zipoli, V., Goretti, B., et al., Apolipoprotein E epsilon 4 allele is not associated with disease course and severity in multiple sclerosis, Acta Neurol. Scand., 2009, vol. 120, no. 6, pp. 439–441. doi 10.1111/j.16000404.2009.01278x

    Article  CAS  PubMed  Google Scholar 

  • Qamar, N. and Fuleihan, R.L., The hyper IgM syndromes, Clin. Rev. Allergy Immunol., 2013, vol. 46, no. 2, pp. 205–215. doi 10.1007/s12016-013-8378-7

    Google Scholar 

  • Qiu, W., Pham, K., James, I., et al., The influence of nonHLA gene polymorphisms and interactions on disease risk in a Western Australian multiple sclerosis cohort, J. Neuroimmunol., 2013, vol. 261, nos. 1–4, pp. 92–97. doi 10.1016/jjneuroim.2013.04.022.

    Article  CAS  PubMed  Google Scholar 

  • Rafiei, M., Zarif Yeganeh, M., Sheikholeslami, S., et al., Apolipoprotein E polymorphisms status in Iranian patients with multiple sclerosis, J. Neurol. Sci., 2012, vol. 320, nos. 1–4, pp. 22–25. doi 10.1016/jjns.2012.05.050

    Article  CAS  PubMed  Google Scholar 

  • Sanna, S., Pitzalis, M., Zoledziewska, M., et al., Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis, Nat. Genet., 2010, vol. 42, no. 6, pp. 495–497. doi 10.1038/ng.584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos, M., Costa, M. do C., Rio, M.E., et al., Genotypes at the APOE and SCA2 loci do not predict the course of multiple sclerosis in patients of Portuguese origin, Mult. Scler., 2004, vol. 10, no. 2. 153–157.

    Article  Google Scholar 

  • Santos, M., Pinto-Basto, J., Rio, M.E., et al., A whole genome screen for association with multiple sclerosis in Portuguese patients, J. Neuroimmunol., 2003, vol. 143, nos. 1–4, pp. 112–115.

    Article  CAS  PubMed  Google Scholar 

  • Savettieri, G., Andreoli, V., Bonavita, S., et al., Apolipoprotein E genotype does not influence the progression of multiple sclerosis, J. Neurol., 2003, vol. 250, no. 9, pp. 1094–1098. doi 10.1007/s00415-003-0163-8

    Article  CAS  PubMed  Google Scholar 

  • Sawcer, S., A new era in the genetic analysis of multiple sclerosis, Curr. Opin. Neurol., 2006, vol. 19, no. 3, pp. 237–241. doi 10.1097/01wco.0000227031.39834.31

    Article  PubMed  Google Scholar 

  • Sawcer, S., The genetic aspects of multiple sclerosis, Ann. Indian Acad. Neurol., 2009, vol. 12, no. 4, pp. 206–214. doi 10.4103/0972-2327.58272

    Article  PubMed  PubMed Central  Google Scholar 

  • Sawcer, S., Ban, M., Maranian, M., et al., A high-density screen for linkage in multiple sclerosis, Am. J. Hum. Genet., 2005, vol. 77, no. 3, pp. 454–467. doi 10.1086/444547

    Article  PubMed  Google Scholar 

  • Sawcer, S., Hellenthal, G., Pirinen, M., et al., Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis, Nature, 2011, vol. 476, no. 7359, pp. 214–219. doi 10.1038/nature10251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sawcer, S., Jones, H.B., Feakes, R., et al., A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22, Nat. Genet., 1996, vol. 13, no. 4, pp. 464–468. doi 10.1038/ng0896-464

    Article  CAS  PubMed  Google Scholar 

  • Schmidt, S., Barcellos, L.F., De Sombre, K., et al., Association of polymorphisms in the apolipoprotein E region with susceptibility to and progression of multiple sclerosis, Am. J. Hum. Genet., 2002, vol. 70, no. 3, pp. 708–717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sedano, M.I., Calmarza, P., Perez, L., and Trejo, J.M., No association of apolipoprotein E epsilon 4 genotype with faster progression or less recovery of relapses in a Spanish cohort of multiple sclerosis, Mult. Scler., 2006, vol. 12, no. 1, pp. 13–18.

    Article  CAS  PubMed  Google Scholar 

  • Sena, A., Couderc, R., Ferret-Sena, V., et al., Apolipoprotein E polymorphism interacts with cigarette smoking in progression of multiple sclerosis, Eur. J. Neurol., 2009, vol. 16, no. 7, pp. 832–837. doi 10.1111/j.14681331.2009.02603x

    Article  CAS  PubMed  Google Scholar 

  • Shi, J., Tu, J.-L., Gale, S.D., et al., APOE e4 is associated with exacerbation of cognitive decline in patients with multiple sclerosis, Cognit. Behav. Neurol., 2011, vol. 24, no. 3, pp. 128–133. doi 10.1097/WNN.0b013e31823380b5

    Article  Google Scholar 

  • Shi, J., Zhao, C.B., Vollmer, T.L., et al., APOE epsilon 4 allele is associated with cognitive impairment in patients with multiple sclerosis, Neurology, 2008, vol. 70, no. 3, pp. 185–190. doi 10.1212/01wnl. 0000264004.62612.44

    Article  CAS  PubMed  Google Scholar 

  • Singer, N.G., Fox, D.A., Haqqi, T.M., et al., CD6: expression during development, apoptosis and selection of human and mouse thymocytes, Int. Immunol., 2002, vol. 14, no. 6, pp. 585–597.

    Article  CAS  PubMed  Google Scholar 

  • Sokolova, E.A., Malkova, N.A., Korobko, D.S., et al., Association of SNPs of CD40 gene with multiple sclerosis in Russians, PLoS One, 2013, vol. 8, no. 4. p. e61032. doi 10.1371/journalpone.0061032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song, G.G., Choi, S.J., Ji J.D., and Lee, Y.H., Genomewide pathway analysis of a genome-wide association study on multiple sclerosis, Mol. Biol. Rep., 2013, vol. 40, no. 3, pp. 2557–2564. doi 10.1007/s11033012-2341-1

    Article  CAS  PubMed  Google Scholar 

  • Tamam, Y., Tasdemir, N., Yalman, M., and Tamam, B., Association of apolipoprotein E genotypes with prognosis in multiple sclerosis, Eur. Rev. Med. Pharmacol. Sci., 2011, vol. 15, no. 10, pp. 1122–1130.

    CAS  PubMed  Google Scholar 

  • Tiffin, N., Kelso, J.F., Powell, A.R., et al., Integration of text and data-mining using ontologies successfully selects disease gene candidates, Nucleic Acids Res., 2005, vol. 33, no. 5, pp. 1544–1552. doi 10.1093/nar/gki296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, K., Li, M., and Bucan, M., Pathway-based approaches for analysis of genome-wide association studies, Am. J. Hum. Genet., 2007, vol. 81, no. 6, pp. 1278–1283. doi 10.1086/522374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weatherby, S.J., Mann, C.L., Davies, M.B., et al., Polymorphisms of apolipoprotein E; outcome and susceptibility in multiple sclerosis, Mult. Scler., 2000a, vol. 6, no. 1, pp. 32–36.

    Article  CAS  PubMed  Google Scholar 

  • Weatherby, S.J., Mann, C.L., Fryer, A.A., et al., No association between the APOE epsilon 4 allele and outcome and susceptibility in primary progressive multiple sclerosis, J. Neurol., Neurosurg., Psychiatry, 2000b, vol. 68, no. 4, p. 532.

    Article  Google Scholar 

  • Willer, C.J., Dyment, D.A., Risch, N.J., et al., Twin concordance and sibling recurrence rates in multiple sclerosis, Proc. Natl. Acad. Sci. U.S.A., 2003, vol. 100, no. 22, pp. 12877–12882. doi 10.1073/pnas.1932604100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, Q., Khoury, M.J., Friedman, J., et al., How many genes underlie the occurrence of common complex diseases in the population? Int. J. Epidemiol., 2005, vol. 34, no. 5, pp. 1129–1137. doi 10.1093/ije/dyi130

    Article  PubMed  Google Scholar 

  • Yeo, T.W., Roxburgh, R., Maranian, M., et al., Refining the analysis of a whole genome linkage disequilibrium association map: the United Kingdom results, J. Neuroimmunol., 2003, vol. 143, nos. 1–4, pp. 53–59.

    Article  CAS  PubMed  Google Scholar 

  • Zakrzewska-Pniewska, B., Styczynska, M., Podlecka, A., et al., Association of apolipoprotein E and myeloperoxidase genotypes to clinical course of familial and sporadic multiple sclerosis, Mult. Scler., 2004, vol. 10, no. 3, pp. 266–271.

    Article  CAS  PubMed  Google Scholar 

  • Zwemmer, J.N.P., van Veen, T., van Winsen, L., et al., No major association of ApoE genotype with disease characteristics and MRI findings in multiple sclerosis, Mult. Scler., 2004, vol. 10, no. 3, pp. 272–277.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, pr. Akademika Lavrent’eva 8, Novosibirsk, 630090, Russia

    E. A. Sokolova, U. A. Boyarskikh & M. L. Filipenko

  2. Novosibirsk State University, ul. Pirogova 2, Novosibirsk, 630090, Russia

    E. A. Sokolova, Yu. S. Aulchenko & M. L. Filipenko

  3. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, pr. Akademika Lavrent’eva 10, Novosibirsk, 630090, Russia

    Yu. S. Aulchenko

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  1. E. A. Sokolova
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  2. U. A. Boyarskikh
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  3. Yu. S. Aulchenko
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  4. M. L. Filipenko
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Correspondence to E. A. Sokolova.

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Original Russian Text © E.A. Sokolova, U.A. Boyarskikh, Yu.S. Aulchenko, M.L. Filipenko, 2015, published in Uspekhi Sovremennoi Biologii, 2015, Vol. 135, No. 4, pp. 355–369.

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Sokolova, E.A., Boyarskikh, U.A., Aulchenko, Y.S. et al. Genetics of multiple sclerosis today. Biol Bull Rev 6, 113–125 (2016). https://doi.org/10.1134/S2079086416020080

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