Human T-cell receptor V beta gene polymorphism and multiple sclerosis.
Population-based genetic associations have been reported between RFLPs detected with probes corresponding to the genes encoding the beta chain of the T-cell receptor for antigen (TCRB) and a variety of autoimmune disorders. In the case of multiple sclerosis (MS), these studies have localized a putative disease-associated gene to a region of approximately 110 kb in length, located within the TCRB locus. In the current study, all 14 known TCRBV (variable region) genes within the region of localization were mapped and identified. The nucleotide sequences of these genes were determined in a panel of six MS patients and six healthy controls, who were human-leukocyte antigen and TCRB-RFLP haplotype matched. Nine of the 14 TCRBV genes studied showed evidence of polymorphism. PCR-based assays for each of these polymorphic genes were developed, and allele and genotype frequencies were determined in a panel of DNA samples from 48 MS patients and 60 control individuals. No significant differences in allele, genotype, or phenotype frequencies were observed between the MS patients and controls for any of the 14 TCRBV-gene polymorphisms studied. In light of the extensive linkage disequilibrium across the region studied, the saturating numbers of polymorphisms examined, and the direct sequence analysis of all BV genes in the region, these results suggest that it is unlikely that germ-line polymorphism in the TCRBV locus makes a major contribution to MS susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)
Wei
S
S
Virginia Mason Research Center, Seattle, WA 98101, USA.
Charmley
P
P
Birchfield
R I
RI
Concannon
P
P
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D008040:Genetic Linkage; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*
D016693:Receptors, Antigen, T-Cell, alpha-beta