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Members 6B and 14 of the TNF receptor superfamily in multiple sclerosis predisposition

Genes & Immunity volume 12, pages 145–148 (2011)Cite this article

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Abstract

TNFRSF6B and TNFRSF14 genes were recently associated with Crohn's disease and rheumatoid arthritis. TNFRSF14 is known as herpes virus entry mediator (HVEM), and herpes viruses have been involved in the aetiology of multiple sclerosis (MS). MS patients present human herpes virus 6 (HHV6) in active plaques and increased antibody responses to HHV6. We aimed to ascertain the role of these genes in MS susceptibility and to investigate the relationship of the gene encoding the widely expressed HVEM receptor with the active replication of HHV6 found in some MS patients. Genotyping of 1370 Spanish MS patients and 1715 ethnically matched controls was performed. HHV6A DNA levels (surrogate of active viral replication) were analysed in serum of MS patients during a 2-year follow-up. Both polymorphisms were associated with MS predisposition, with stronger effect in patients with HHV6 active replication—TNFRSF6B-rs4809330*A: P=0.028, OR=1.13; TNFRSF14-rs6684865*A: overall P=0.0008, OR=1.2; and HHV6-positive patients vs controls: P=0.017, OR=1.69.

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Acknowledgements

The authors thank Carmen Martínez and M Angel García for their skilful technical assistance. Roberto Alvarez-Lafuente is recipient of a research contract from ‘Fondo de Investigaciones Sanitarias’ (CP07/00273) and Elena Urcelay works for the Fundación para la Investigación Biomédica-Hospital Clínico San Carlos. This work was supported by grants from: Alfonso Martín Escudero Foundation, Fondos Europeos de Desarrollo Regional (FEDER) and Ministerio de Ciencia e Innovación (SAF2006-02023, SAF2009-11491), Junta de Andalucía (P07-CVI-02551), Servicio Andaluz de Salud (PI0168/2007), Plan Andaluz P08-TIC-03717 and Fondo Investigaciones Sanitarias FIS PI07/0353, PI08/1636 and RETICS 2007 (REEM). We acknowledge the International Multiple Sclerosis Genetics Consortium (IMSGC) and the Wellcome Trust Case-Control Consortium (WTCCC) for sharing their data repository.

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Author notes

  1. R Alvarez-Lafuente, V de las Heras, E G de la Concha, O Fernández, R Arroyo, F Matesanz and E Urcelay: Members of the Red Española de Esclerosis Múltiple (REEM), www.reem.es.

  2. F Blanco-Kelly, R Alvarez-Lafuente, A Alcina, F Matesanz and E Urcelay: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Hospital Clínico San Carlos, Madrid, Spain

    F Blanco-Kelly, E G de la Concha & E Urcelay

  2. Department of Neurology, Hospital Clínico San Carlos, Madrid, Spain

    R Alvarez-Lafuente, V de las Heras & R Arroyo

  3. Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain

    A Alcina & F Matesanz

  4. Departamento de Lenguajes y Sistemas Informáticos, Universidad de Granada, Granada, Spain

    M M Abad-Grau

  5. Servicio de Biología Molecular, Hospital Virgen Macarena, Sevilla, Spain

    M Lucas

  6. Instituto de Neurociencias Clínicas, Hospital Regional Universitario Carlos Haya, Málaga, Spain

    O Fernández

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  1. F Blanco-Kelly
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  2. R Alvarez-Lafuente
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  3. A Alcina
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Correspondence to E Urcelay.

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Blanco-Kelly, F., Alvarez-Lafuente, R., Alcina, A. et al. Members 6B and 14 of the TNF receptor superfamily in multiple sclerosis predisposition. Genes Immun 12, 145–148 (2011). https://doi.org/10.1038/gene.2010.42

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  • DOI: https://doi.org/10.1038/gene.2010.42

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