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

S. Schmidt, Margaret A Pericak-Vance, S. Sawcer, L. F. Barcellos, J. Hart, J. Sims, A. M. Prokop, J. van der Walt, C. DeLoa, R. R. Lincoln, J. R. Oksenberg, A. Compston, S. L. Hauser, J. L. Haines, S. G. Gregory

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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.

Original languageEnglish
Pages (from-to)384-392
Number of pages9
JournalGenes and Immunity
Volume7
Issue number5
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

Fingerprint

Virus Internalization
Multiple Sclerosis
Genes
Apolipoproteins E
Introns
Genetic Polymorphisms

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis. / Schmidt, S.; Pericak-Vance, Margaret A; Sawcer, S.; Barcellos, L. F.; Hart, J.; Sims, J.; Prokop, A. M.; van der Walt, J.; DeLoa, C.; Lincoln, R. R.; Oksenberg, J. R.; Compston, A.; Hauser, S. L.; Haines, J. L.; Gregory, S. G.

In: Genes and Immunity, Vol. 7, No. 5, 01.07.2006, p. 384-392.

Research output: Contribution to journalArticle

Schmidt, S, Pericak-Vance, MA, Sawcer, S, Barcellos, LF, Hart, J, Sims, J, Prokop, AM, van der Walt, J, DeLoa, C, Lincoln, RR, Oksenberg, JR, Compston, A, Hauser, SL, Haines, JL & Gregory, SG 2006, 'Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis', Genes and Immunity, vol. 7, no. 5, pp. 384-392. https://doi.org/10.1038/sj.gene.6364311
Schmidt, S. ; Pericak-Vance, Margaret A ; Sawcer, S. ; Barcellos, L. F. ; Hart, J. ; Sims, J. ; Prokop, A. M. ; van der Walt, J. ; DeLoa, C. ; Lincoln, R. R. ; Oksenberg, J. R. ; Compston, A. ; Hauser, S. L. ; Haines, J. L. ; Gregory, S. G. / Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis. In: Genes and Immunity. 2006 ; Vol. 7, No. 5. pp. 384-392.
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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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