title: Revisiting the T-cell receptor alpha/delta locus and possible associations with multiple sclerosis.
abstract: A role for T cells in the pathogenesis of multiple sclerosis (MS) is well supported, evidenced by myriad immunological studies, as well as the unequivocal genetic influence of the major histocompatibility complex (MHC). Despite many attempts, no convincing genetic associations have been made between T-cell receptor (TCR) gene loci and MS. However, these studies may not be definitive because of small sample sizes and under-representative marker coverage of the chromosomal regions being investigated. To explore potential roles between the TCR alpha locus and MS, we have genotyped a large family-based cohort, including 1360 affected individuals and 1659 of their unaffected first-degree relatives, at 40 single-nucleotide polymorphism (SNP) markers within the TCR alpha/delta locus. This represents the largest TCR alpha-MS study to date. From this screen, we identified three potential loci of interest in TCR alpha variable and constant gene regions using the transmission disequilibrium test. Although SNPs implicating each of these regions of interest will require genotyping in independent replication cohorts, these findings suggest a role for TCR gene polymorphisms in MS susceptibility. In the context of these findings we review the evidence.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: C T
authors.initials: CT
authors.lastname: Watson
authors.forename: A E
authors.initials: AE
authors.lastname: Para
authors.forename: M R
authors.initials: MR
authors.lastname: Lincoln
authors.forename: S V
authors.initials: SV
authors.lastname: Ramagopalan
authors.forename: S M
authors.initials: SM
authors.lastname: Orton
authors.forename: K M
authors.initials: KM
authors.lastname: Morrison
authors.forename: L
authors.initials: L
authors.lastname: Handunnetthi
authors.forename: A E
authors.initials: AE
authors.lastname: Handel
authors.forename: M J
authors.initials: MJ
authors.lastname: Chao
authors.forename: J
authors.initials: J
authors.lastname: Morahan
authors.forename: A D
authors.initials: AD
authors.lastname: Sadovnick
authors.forename: F
authors.initials: F
authors.lastname: Breden
authors.forename: G C
authors.initials: GC
authors.lastname: Ebers
mesh_terms: D015331:Cohort Studies; D019673:Genes, T-Cell Receptor alpha; D019676:Genes, T-Cell Receptor delta; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta