Susceptibility for multiple sclerosis is determined, in part, by inheritance of a 175-kb region of the TcR Vβ chain locus and HLA class II genes

Beall, Steven S.; Biddison, William E.; McFarlin, Dale E.; McFarland, Henry F.; Hood, Leroy

doi:10.1016/0165-5728(93)90163-s

Cited by 94 publications

(19 citation statements)

References 40 publications

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“…The haplotype was overtransmitted but not significantly so (transmitted 19 times vs 12 times). The three loci do map to a previously reported restriction enzyme defined region of association, 10 and further investigation is warranted.…”

Section: Discussionmentioning

confidence: 79%

“…5 However, the finding is not consistent as other groups have not found linkage in the same region. [6][7][8] Case-control studies involving TCR b polymorphisms have reported associations with MS, [9][10][11][12] with other positive associations observed once the samples were stratified for the presence of HLA DR2 antigens. 13,14 This stratification has been extended to include those patients who are DR2 positive and suffering from a relapsingprogressive course of multiple sclerosis.…”

Section: Introductionmentioning

confidence: 99%

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TCR β polymorphisms and multiple sclerosis

et al. 2004

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A total of 267 families with two or more siblings with multiple sclerosis (MS) were genotyped with 14 restriction fragment length polymorphisms at the TCR b locus. A nonparametric linkage analysis of the data showed no evidence for linkage to this locus (mlod ¼ 0.11). No significant allelic or haplotype transmissions were observed in the total sample of 565 patients. After stratification for the presence of HLA DRB1*15, an association was observed between the BV25S1*1-BV26S1*1-BV2S1*1 haplotype and MS (P ¼ 0.00089). This was not significant upon correction for multiple comparisons. It was also not significant when the haplotype frequency in affected individuals was compared to a normal control sample (P ¼ 0.77). Furthermore, the associated haplotype was followed-up in an independent sample of 97 nuclear families with a single DRB1*15-positive child with MS. The BV25S1*1-BV26S1*1-BV2S1*1 haplotype did not show significant evidence for transmission distortion but the same trend was seen (P ¼ 0.21). There were no significant associations observed in the DRB1*15-negative patients and no detectable difference was seen in the DRB1*15-positive BV25S1*1-BV26S1*1-BV2S1*1 association when comparing different subgroups based on clinical course of MS. These results show no evidence for linkage and fail to establish an association between MS susceptibility and the TCR b locus.

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Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

TCR β polymorphisms and multiple sclerosis

et al. 2004

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“…The T cell receptor (TCR) gene was also found increased in expression as well as the zeta chain associated protein kinase (ZAP70). TCR is essential for T cell mediated immune response and has been implicated in MS susceptibility (Beall et al, 1993). ZAP70 is directly implicated in TCR induced T cell activation (Chan et al, 1992).…”

Section: Major Peripheral Blood Mononuclear Cell Gene Expression Micrmentioning

confidence: 99%

Gene Expression Pattern Characterises Development of Multiple Sclerosis

Tajouri¹,

Brenu²,

Ashton³

et al. 2013

Genes and Autoimmunity - Intracellular Signaling and Microbiome Contribution

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“…29 Although a role for T cells in MS seems indisputable, no consistent and replicable genetic associations have been made between polymorphisms at T-cell receptor (TCR) loci and MS, despite suggestive links to both TCR beta and alpha genes. [30][31][32][33][34][35][36][37][38][39][40][41][42][43] A possible explanation for the observed inconsistency between studies investigating TCR gene loci and MS could be a lack of power to discover associations, because of small sample sizes and unrepresentative marker coverage of the TCR regions investigated. Given these limitations, it is reasonable to conclude that, although no strong associations have been identified within the TCR loci, these regions cannot be unequivocally ruled out on the basis of previous studies alone.…”

Section: Introductionmentioning

confidence: 99%

“…Conflicting results have also been observed for the TCR beta locus and MS, [40][41][42] although these will not be discussed in detail here. The exact reasons for the inconsistencies described above are unknown.…”

mentioning

confidence: 97%

Revisiting the T-cell receptor alpha/delta locus and possible associations with multiple sclerosis

et al. 2011

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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.

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Susceptibility for multiple sclerosis is determined, in part, by inheritance of a 175-kb region of the TcR Vβ chain locus and HLA class II genes

Cited by 94 publications

References 40 publications

TCR β polymorphisms and multiple sclerosis

TCR β polymorphisms and multiple sclerosis

Gene Expression Pattern Characterises Development of Multiple Sclerosis

Revisiting the T-cell receptor alpha/delta locus and possible associations with multiple sclerosis

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