T cell receptor α chain polymorphisms in multiple sclerosis

Hashimoto, L.; Mak, Tak W.; Ebers, George C.

doi:10.1016/0165-5728(92)90211-3

Cited by 44 publications

(12 citation statements)

References 25 publications

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“…37 Subsequent association studies investigating the role of TCR alpha polymorphisms in Canadian, Swedish, Belgian and Northern Irish populations with equivalent or larger sample sizes compared with those above were unable to replicate these findings. 34,35,39,40 Also, in two of these studies, no interaction between HLA-DR2 and TRA genotypes was observed. 35,39 Additionally, Hillert et al…”

Section: T-cell Receptorsmentioning

confidence: 99%

“…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%

“…Compared with what would be expected by random segregation, they found no indication for haplotype sharing between three TRAV and TRD region RFLP polymorphisms. 34 Finally, no support for linkage was found in two separate siblingpair cohorts from the British Isles. 38 In Eoli et al, 38 49 pairs were screened using two RFLP assays and 82 additional pairs were screened at a single microsatellite marker.…”

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confidence: 99%

“…Using RFLP and a TRA probe, Lynch et al 36 screened 99 individuals from 44 multiplex families (USA), including 34 individuals with definite MS, 26 of which were HLA-DR2-positive and identified no evidence for linkage. Hashimoto et al, 34 in addition to their association-based method, assessed haplotype sharing at the TCR alpha locus in 30 concordant MS sibling pairs using identity by descent. Compared with what would be expected by random segregation, they found no indication for haplotype sharing between three TRAV and TRD region RFLP polymorphisms.…”

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confidence: 99%

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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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Section: T-cell Receptorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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

et al. 2011

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“…Despite an initial positive association of a TCR a rearrangement in multiple sclerosis brains (MS), 1 most studies have failed to demonstrate an association with germline polymorphisms and MS. 2,3 The same is not true for the TCR b receptor variable chain locus. The locus has been linked to MS in a small sample of affected sibs, 4 and an MS genome scan observed evidence for increased haplotype sharing at 7q35.…”

Section: Introductionmentioning

confidence: 99%

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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Multiple Sclerosis

Kálmán¹

2007

Neuroimmunology in Clinical Practice

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T cell receptor α chain polymorphisms in multiple sclerosis

Cited by 44 publications

References 25 publications

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

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

TCR β polymorphisms and multiple sclerosis

Multiple Sclerosis

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