The etiology of multiple sclerosis: genetic evidence for the involvement of the human endogenous retrovirus HERV-Fc1

We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or alm...

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Published in:	PloS one Vol. 6; no. 2; p. e16652
Main Authors:	Nexø, Bjørn A, Christensen, Tove, Frederiksen, Jette, Møller-Larsen, Anné, Oturai, Annette B, Villesen, Palle, Hansen, Bettina, Nissen, Kari K, Laska, Magdalena J, Petersen, Trine S, Bonnesen, Sandra, Hedemand, Anne, Wu, Tingting, Wang, Xinjie, Zhang, Xiuqing, Brudek, Tomasz, Maric, Romana, Søndergaard, Helle B, Sellebjerg, Finn, Brusgaard, Klaus, Kjeldbjerg, Anders L, Rasmussen, Henrik B, Nielsen, Anders L, Nyegaard, Mette, Petersen, Thor, Børglum, Anders D, Pedersen, Finn S
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 02-02-2011 Public Library of Science (PLoS)
Subjects:	Alleles Analysis Biology Case-Control Studies Cohort Studies Deoxyribonucleic acid Development and progression Disease Disease control DNA DNA, Viral - analysis DNA, Viral - physiology Endogenous retroviruses Endogenous Retroviruses - genetics Endogenous Retroviruses - physiology Etiology Etiology (Medicine) Female Genes Genetic aspects Genetic engineering Genetic Predisposition to Disease Genomes Herpes viruses Heterozygote Hospitals Human endogenous retrovirus Humans Leukemia Linkage Disequilibrium Loci Male Medical research Medicine Molecular biology Monkeys & apes Multiple sclerosis Multiple Sclerosis - etiology Multiple Sclerosis - genetics Multiple Sclerosis - virology Neurology Odds Ratio Polymorphism, Single Nucleotide - physiology Single nucleotide polymorphisms Single-nucleotide polymorphism Studies Twins Aarhus Denmark
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Summary:	We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Conceived and designed the experiments: BAN FSP TC AML TP. Performed the experiments: BH KKN MJL TSP SB AH TW XW XZ. Analyzed the data: BAN PV TW XW XZ ALK ALN MN ADB. Contributed reagents/materials/analysis tools: TC JF AML ABO TB RM HBS FS KB HBR TP. Wrote the paper: BAN.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0016652