Association studies in multiple sclerosis

Ebers, George C.; Sadovnick, A. Dessa

doi:10.1016/0165-5728(94)90021-3

Cited by 29 publications

(9 citation statements)

References 31 publications

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“…An association with the development of MS is apparent with both class I (A3 and B7) and class II (DR2 and DQW1) genes depending on the ethnicity of the groups studied (reviewed by Ebers and Sadovnick [14]). The role of various class I or class II genes in the progression of MS has been studied, but no consensus has been reached as to whether particular alleles are correlated with long-term disability.…”

Section: Discussionmentioning

confidence: 99%

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Expression of the human histocompatibility leukocyte antigen DR3 transgene reduces the severity of demyelination in a murine model of multiple sclerosis.

et al. 1998

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The role of various MHC genes in determining the progression of multiple sclerosis (MS) remains controversial. The HLA-DR3 gene has been associated with benign relapsing MS in some genetic epidemiologic studies, but with disease progression in others. We induced demyelination in highly susceptible B10.M and B10.Q mice expressing the DR3 (HLA-DRB1*0301) transgene to determine directly the effects of a human transgene by infecting them with Theiler's murine encephalomyelitis virus (TMEV). DR3 ϩ mice experienced a dramatic reduction in the extent and severity of demyelination compared with DR3 Ϫ littermate controls, whereas anti-TMEV antibody titers, delayed-type hypersensitivity responses, and levels of infectious virus, virus antigen, and virus RNA were similar in both groups. To address a possible mechanism of how the human transgene is reducing virus-induced demyelination, we analyzed cytokine expression in the lesions and also determined whether B10.

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Section: Discussionmentioning

confidence: 99%

“…Many of the associations made to date are not absolute and vary according to ethnic group. For example, among individuals of Northern European origin, strong associations have been identified between particular MHC class I (HLA A3 and B7) and class II (DR2 and DQW1) alleles and the development of MS (reviewed by Ebers and Sadovnick [14]). …”

Section: Introductionmentioning

confidence: 99%

Expression of the human histocompatibility leukocyte antigen DR3 transgene reduces the severity of demyelination in a murine model of multiple sclerosis.

et al. 1998

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“…Many past studies were not family-based and the results may be prone to mismatching of cases and controls while others have too small numbers to detect a mild-moderate association. 22 Here we used a familybased and case-control study design in tandem and found no evidence for linkage, no evidence for association in the case-control study design and some mildly suggestive, but not significant, evidence for transmission distortion in a subset of patients.…”

Section: Discussionmentioning

confidence: 83%

“…[16][17][18][19][20][21] The reasons for these discrepant results are many and may include population stratification, small sample sizes, clinical heterogeneity within the MS patient sample, informativity of the selected markers or simply the reporting of false-positive results. 22 The low reproducibility of positive genetic association studies has drawn appropriate comment. 23 …”

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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“…Eleven T-cell clones were used, each restricted to HLA alleles previously described in association with MS susceptibility (Ho et al, 1982;Hauser et al, 1989;Ebers and Sadovnick, 1994;Voskuhl et al, 1996). Eight of the 11 T-cell clones were derived fiom the peripheral blood of MS patients, and each of the eight recognized the 83-99 sequence within HOG 7.…”

Section: Discussionmentioning

confidence: 99%