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Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis

Genes & Immunity volume 7, pages 384–392 (2006)Cite this article

Abstract

Discrepant findings have been reported regarding an association of the apolipoprotein E (APOE) gene with the clinical course of multiple sclerosis (MS). To resolve these discrepancies, we examined common sequence variation in six candidate genes residing in a 380-kb genomic region surrounding and including the APOE locus for an association with MS severity. We genotyped at least three polymorphisms in each of six candidate genes in 1540 Caucasian MS families (729 single-case and multiple-case families from the United States, 811 single-case families from the UK). By applying the quantitative transmission/disequilibrium test to a recently proposed MS severity score, the only statistically significant (P=0.003) association with MS severity was found for an intronic variant in the Herpes Virus Entry Mediator-B Gene (PVRL2). Additional genotyping extended the association to a 16.6 kb block spanning intron 1 to intron 2 of the gene. Sequencing of PVRL2 failed to identify variants with an obvious functional role. In conclusion, the analysis of a very large data set suggests that genetic polymorphisms in PVRL2 may influence MS severity and supports the possibility that viral factors may contribute to the clinical course of MS, consistent with previous reports.

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Acknowledgements

We thank all patients and families who generously participated in this study. We thank the collaborating clinics and physicians for referring individuals to the study. This research was supported by National Institutes of Health Grants NS32830, NS26799 and NS049477.

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Authors and Affiliations

  1. Center for Human Genetics, Duke University Medical Center, Durham, NC, USA

    S Schmidt, M A Pericak-Vance, J Hart, J Sims, A M Prokop, J van der Walt & S G Gregory

  2. Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

    S Sawcer & A Compston

  3. Division of Epidemiology, School of Public Health, University of California at Berkeley, Berkeley, CA, USA

    L F Barcellos

  4. Department of Neurology, School of Medicine, University of California San Francisco, San Francisco, CA, USA

    L F Barcellos, C DeLoa, R R Lincoln, J R Oksenberg & S L Hauser

  5. Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA

    J L Haines

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Schmidt, S., Pericak-Vance, M., Sawcer, S. et al. Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis. Genes Immun 7, 384–392 (2006). https://doi.org/10.1038/sj.gene.6364311

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