Subscribe to RSS
DOI: 10.1590/0004-282X20160100
The immunogenetics of multiple sclerosis. The frequency of HLA-alleles class 1 and 2 is lower in Southern Brazil than in the European population
Imunogenética na esclerose múltipla. A frequência dos alelos HLA classe 1 e 2 no sul do Brasil são menores que da população EuropeiaABSTRACT
Objective To study the HLA of class 1and 2 in a multiple sclerosis (MS) population to verify the susceptibility for the disease in the Southern Brazil.
Methods We analyzed patients with MS and controls, by direct sequencing of the genes related to HLA DRB1, DQB1, DPB1, A, B and C alleles with high resolution techniques.
Results We found a lower frequency of all HLA alleles class 1 and 2 in MS and controls comparing to the European population. Several alleles had statistical correlation, but after Bonferroni correction, the only allele with significance was the HLA-DQB1*02:03, which has a positive association with MS.
Conclusions Our data have different frequency of HLA-alleles than the previous published papers in the Southeast Brazil and European population, possible due to several ethnic backgrounds.
RESUMO
Objetivo Estudo do HLA classes 1 e 2 em pacientes com esclerose múltipla (EM) a fim de verificar a susceptibilidade para a doença em uma população do Sul do Brasil.
Métodos Foram analisados por sequenciamento direto de alta resolução os genes relacionados com os HLA DRB1, DQB1, DPB1, A, B e C em casos de EM comparados com uma população controle normal.
Resultados Foi encontrado uma frequência menor dos alelos dos HLA classe 1 e 2 nos casos de EM e controles quando comparado com a população Europeia. Diversos alelos mostraram correlação estatística, mas depois da correção de Bonferroni, somente o alelo do HLA-DQB1*02:03 foi positivo para a EM.
Conclusões Encontramos frequência diferente dos alelos do HLA relatados previamente nos Sudeste do Brasil e Europeus, possivelmente devido a origem étnica diferente da população estuda.
Support:
Support: This study was supported in part by Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Serono and Biogen.
Publication History
Received: 18 May 2016
Accepted: 25 May 2016
Article published online:
06 September 2023
© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil
-
References
- 1 Murphy K, Travers P, Walport M. Janeways’s immunobiology. 7th ed. New York: Garland Science; 2008. p. 196-212.
- 2 Ramagopalan SV, Ebers GC. Multiple sclerosis: major histocompatibility complexity and antigen presentation. Genome Med. 2009;1(11):105. doi:10.1186/gm105
- 3 Barcellos LF, Sawcer S, Ramsay PP, Baranzini SE, Thomson G, Briggs F et al. Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis. Hum Mol Genet. 2006;15(18):2813-24. doi:10.1093/hmg/ddl223
- 4 Lincoln MR, Ramagopalan SV, Chao MJ, Herrera BM, Deluca GC, Orton SM et al. Epistasis among HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci determines multiple sclerosis susceptibility. Proc Natl Acad Sci USA. 2009;106(18):7542-7. doi:10.1073/pnas.0812664106
- 5 Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L et al. Genetic risk and a primary role for cell-mediated immune mechanism in multiple sclerosis. Nature. 2011;476(7359):214-9. doi:10.1038/nature10251
- 6 Marrosu MG, Murru R, Murru MR, Costa G, Zavattari P, Whalen M et al. Dissection of the HLA association with multiple sclerosis in the founder isolated population of Sardinia. Hum Mol Genet. 2001;10(25):2907-26. doi:10.1093/hmg/10.25.2907
- 7 Fernández O, R-Antigüedad A, Pinto-Medel MJ, Mendibe MM, Acosta N, Oliver B et al. HLA class II alleles in patients with multiple sclerosis in the Biscay province (Basque Country, Spain). J Neurol. 2009;256(12):1977-88. doi:10.1007/s00415-009-5223-2
- 8 McGuigan C, McCarthy A, Quigley C, Bannan L, Hawkins SA, Hutchinson M. Latitudinal variation in the prevalence of multiple sclerosis in Ireland, an effect of genetic diversity. J Neurol Neurosurg Psychiatry. 2004;75(4):572-6. doi:10.1136/jnnp.2003.012666
- 9 Aláez C, Corona T, Ruano L, Flores H, Loyola M, Gorodezky C. Mediterranean and Amerindian MHC class II alleles are associated with multiple sclerosis in Mexicans. Acta Neurol Scand. 2005;112(5):317-22. doi:10.1111/j.1600-0404.2005.00493.x
- 10 Caballero A, Alvés-León S, Papais-Alvarenga R, Fernández O, Navarro G, Alonso A. DQB1*0602 confers genetic susceptibility to multiple sclerosis in Afro-Brazilians. Tissue Antigens. 1999;54(5):524-6. doi:10.1034/j.1399-0039.1999.540511.x
- 11 Link J, Kockum I, Lorentzen AR, Lie BA, Celius EG, Westerlind H et al. Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis. PLoS One. 2012;7(5):e36779. doi:10.1371/journal.pone.0036779
- 12 Bergamaschi L, Ban M, Barizzone N, Leone M, Ferrante D, Fasano ME et al. Association of HLA class I markers with multiple sclerosis in the Italian and UK population: evidence of two independent protective effects. J Med Genet. 2011;48(7):485-92. doi:10.1136/jmg.2010.080721
- 13 Yeo TW, De Jager PL, Gregory SG, Barcellos LF, Walton A, Goris A et al. A second major histocompatibility complex susceptibility locus for multiple sclerosis. Ann Neurol. 2007;61(3):228-36. doi:10.1002/ana.21063
- 14 Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278-86. doi:10.1212/WNL.20160100201601000560
- 15 Cree BA, Rioux JD, McCauley JL, Gourraud PA, Goyette P, McElroy J et al. A major histocompatibility Class I locus contributes to multiple sclerosis susceptibility independently from HLA-DRB1*15:01. PLoS One. 2010;5(6):e11296. doi:10.1371/journal.pone.0011296
- 16 Ballerini C, Guerini FR, Rombolà G, Rosati E, Massacesi L, Ferrante P et al. HLA-multiple sclerosis association in continental Italy and correlation with disease prevalence in Europe. J Neuroimmunol. 2004;150(1-2):178-85. doi:10.1016/j.jneuroim.2004.01.015
- 17 Mack SJ, Tu B, Lazaro A, Yang R, Lancaster AK, Cao K et al. HLA-A; -B, -C, -DRB1 allele and haplotype frequencies distinguish Eastern European Americans from the general European American population. Tissue Antigens. 2009;73(1):17-32. doi:10.1111/j.1399-0039.2008.01151.x
- 18 Probst CM, Bompeixe EP, Pereira NF, Dalalio MM, Visentainer JE, Tsuneto LT et al. HLA polymorphism and evaluation of European, African, and Amerindian contribution to the white and mulatto population from Paraná, Brazil. Hum Biol. 2000;72(4):597-617. doi:
- 19 Alves-Leon SV, Papais-Alvarenga R, Magalhães M, Alvarenga M, Thuler LCS, Fernandez y Fernandez O. Ethnicity-dependent association of HLA DRB1-DQA1-DQB1 alleles in Brazilian multiple sclerosis patients. Acta Neurol Scand. 2007;115(5):306-11. doi:10.1111/j.1600-0404.2006.00750.x
- 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(1-2):118-24. doi:10.1016/j.jneuroim.2007.06.009
- 21 Paradela ER, Alves-Leon SV, Figueiredo AL, Pereira VC, Malfetano F, Mansur LF et al. The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females. Arq Neuropsiquiatr. 2015;73(4):283-8. doi:10.1590/0004-282X20150012
- 22 Cocco E, Murru R, Costa G, Kumar A, Pieroni E, Melis C et al. Interaction between HLA-DRB1-DQB1 haplotypes in Sardinian multiple sclerosis population. PLoS One. 2013;8(4):e59790. doi:10.1371/journal.pone.0059790
- 23 Kollaee A, Ghaffarpor M, Ghlichnia HA, Ghaffari SH, Zamani M. The influence of the HLA-DRB1 and HLA-DQB1 allele heterogeneity on disease risk and severity in Iranian patients with multiple sclerosis. Int J Immunogenet. 2012;39(5):414-22. doi:10.1111/j.1744-313X.2012.01104.x
- 24 Serjeantson SW, Gao X, Hawkins BR, Higgins DA, Yu YL. Novel HLA-DR2-related haplotypes in Hong Kong Chinese implicate the DQB1*0602 allele in susceptibility to multiple sclerosis. Eur J Immunogenet. 1992;19(1-2):11-9. doi:10.1111/j.1744-313X.1992.tb00043.x
- 25 Rojas OL, Rojas-Villarraga A, Cruz-Tapias P, Sánchez JL, Suárez-Escudero JC, Patarroyo MA et al. HLA class II polymorphism in Latin American patients with multiple sclerosis. Autoimmun Rev. 2010;9(6):407-13. doi:10.1016/j.autrev.2009.11.001
- 26 Patsopoulos NA, Barcellos LF, Hintzen RQ, Schaefer C, van Duijn CM, Noble JA et al. Fine-mapping the genetic association of the major histocompatibility complex in multiple sclerosis: HLA and non-HLA effects. PLoS Genetics. 2013;9(11):e1003926. doi:10.1371/journal.pgen.1003926
- 27 Dekker JW, Easteal S, Jakobsen IB, Gao X, Stewart GJ, Buhler MM et al. HLA-DPB1 alleles correlate with risk for multiple sclerosis in Caucasoid and Cantonese patients lacking the high-risk DQB1*0602 allele. Tissue Antigens. 1993;41(1):31-6. doi:10.1111/j.1399-0039.1993.tb01974.x
- 28 Wu XM, Wang C, Zhang KN, Lin AY, Kira J, Hu GZ et al. Association of susceptibility to multiple sclerosis in Southern Han Chinese with HLA-DRB1, -DPB1 alleles and DRB1-DPB1 haplotypes: distinct from other populations. Mult Scler. 2009;15(12):1422-30. doi:10.1177/1352458509345905
- 29 Healy BC, Liguori M, Tran D, Chitnis T, Glanz B, Wolfish C et al. HLA B*44: protective effects in MS susceptibility and MRI outcome measures. Neurology. 2010;75(7):634-40. doi:10.1212/WNL.0b013e3181ed9c9c
- 30 Instituto Brasileiro de Geografia e Estatística – IBGE. Brasil: 500 anos de povoamento. Rio de Janeiro: Centro de Documentação e Disseminação de Informações; 2007.
- 31 Pena SD, Di Pietro G, Fuchshuber-Moraes M, Genro JP, Hutz MH, Kehdy FS et al. The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected. PLoS One. 2011;6(2):e17063. doi:10.1371/journal.pone.0017063
- 32 Berg-Hansen P, Moen SM, Sandvik L, Harbo HF, Bakken IJ, Stoltenberg C et al. Prevalence of multiple sclerosis among immigrants in Norway. Mult Scler. 2015;21(6):695-702. doi:10.1177/1352458514554055
- 33 Bhargava P, Mowry EM. Gut microbiome and multiple sclerosis. Curr Neurol Neurosci Rep. 2014;14(10):492. doi:10.1007/s11910-014-0492-2
- 34 O’Gorman C, Lucas R, Taylor B. Environmental risk factors for multiple sclerosis: a review with a focus on molecular mechanisms. Int J Mol Sci. 2012;13(9):11718-52. doi:10.3390/ijms130911718
- 35 Pierrot-Deseilligny C, Souberbielle JC. Contribution of vitamina D insufficiency to the pathogenesis of multiple sclerosis. Ther Adv Neurol Disorder. 2013;6(2):81-116. doi:10.1177/1756285612473513