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

• Published in: Genes and immunity Vol. 7; no. 5; pp. 384 - 392
• Main Authors: Schmidt, S, Pericak-Vance, M 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
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-07-2006
• Subjects: 3' Untranslated Regions; 5' Untranslated Regions; Adult; Age Distribution; Age of Onset; Alleles; Apolipoprotein E; European Continental Ancestry Group; Exons; Female; Gene polymorphism; Genes; Genetic aspects; Genetic Variation; Genotyping; Health aspects; Herpes viruses; Herpesvirus; Herpesviruses; Humans; Introns; Linkage Disequilibrium; Male; Multiple sclerosis; Multiple Sclerosis - epidemiology; Multiple Sclerosis - genetics; Multiple Sclerosis - pathology; Polymorphism, Single Nucleotide; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor, Member 14; Receptors, Virus - genetics; Risk factors; Severity of Illness Index; Statistical analysis; United Kingdom - epidemiology; United States - epidemiology; United States
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/sj.gene.6364311

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 1,540 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.