Genetics and transcriptomicsSaturday, October 13, 2007, 15:30 - 17:00
PVRL2 and APOE polymorphisms and severity of multiple sclerosis M. Matiello, B. Weinshenker, D. Hebrink, E. Atkinson, O. Kantarci (Rochester, USA)
Objective: To assess the association of PVRL2 polymorphisms and PVRL2/APOE haplotypes with MS severity in a well characterized population-based group of MS patients
Background: Recently, a polymorphism of the herpesvirus entry mediator-B gene (poliovirus receptor like-2 or PVRL2) on chromosome 19q13 which encodes one of the plasma membrane components of adherens junctions that is implicated in inter-cellular adhesion and entry of neurotropic viruses to the brain has been associated with variation in MS disease severity (Schmidt et al. Genes Immun 2006). A nearby gene, APOE (19q13.2), that may mitigate neurotoxicity and enhance repair in diverse neurological disorders, has also been implicated. Conflicting data exist regarding the associations of both genes with MS severity.
Design/Methods: The SNPs rs1871047, rs394221 and rs3745150 were selected from the PVRL2 gene based on association (rs394221), location and sufficient frequencies to generate robust haplotypes. 219 MS patientsí DNA samples were genotyped for those SNPs through the restriction fragment length polymorphism technique. An extended haplotype analysis was generated with previously studied APOE genotypes (SNPs rs405509, rs429358, rs449647 and rs769446) using an expectation maximization algorithm (Schaid et al, Am J Hum Genet 2002). The ranked severity scores and time to reach EDSS 6 were used to assess MS outcome.
Results: Neither individual PVRL2 SNPs rs1871047 (p=0.8), rs3745150 (p=0.5) and rs394221 (p=0.3), nor the haplotypes imputed using these and APOE SNPS were associated with the severity measurements.
Conclusions/Relevance: We did not confirm an allelic association of a sequence variation of PVRL2 and severity of MS in a population-based cohort with in Olmsted County MN. The previously observed associations with APOE in the same population does not extend to PVRL2.