MULTIPLE-SCLEROSIS SUSCEPTIBILITY - POPULATION AND TWIN STUDY OF POLYMORPHISMS IN THE T-CELL RECEPTOR BETA-GENE AND GAMMA-GENE REGION

被引:9
作者
BRIANT, L [1 ]
AVOUSTIN, P [1 ]
CLAYTON, J [1 ]
MCDERMOTT, M [1 ]
CLANET, M [1 ]
CAMBONTHOMSEN, A [1 ]
机构
[1] CHU PURPAN,CTR RECH POLYMORPHISME GENET POPULAT HUMAINES,CRPG,CNRS,UPR 8291,F-31300 TOULOUSE,FRANCE
关键词
MULTIPLE SCLEROSIS (MS); RESTRICTION FRAGMENT LENGTH POLYMORPHISMS (RFLP); T-CELL RECEPTOR GENES; TWIN STUDIES;
D O I
10.3109/08916939309004841
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Multiple sclerosis (MS) is a demyelinating auto-immune disease of the central nervous system with a suspected genetic component. Previous publications have demonstrated that MS susceptibility is influenced by Major Histocompatibility Complex (MHC) genes and recent studies have focused on additional susceptibility genes. The accumulation of activated T-cells in demyelinating MS lesions, the possible auto-immune mechanism of this disease and the functional relationship between MHC and T cell receptor (TCR) molecules support the hypothesis that TCR genes are good candidates to influence MS development. Published results in this domain are conflicting and still a matter of controversy. In the present study we analysed the influence of Vbeta, Cbeta, PlambdaG3 and Vgamma gene polymorphisms defined by Restriction Fragments Length Polymorphism (RFLP) on 48 pairs of monozygotic and dizygotic twins with at least one of each pair affected, and also in 63 unrelated MS patients for Vgamma gene polymorphism. These results have been compared with those in the non affected twins and with data from a control group (Beall et al., 1989) regarding Cbeta and Vbeta polymorphisms and with a local control population for Vgamma. No significant correlation between Cbeta, Vgamma or PlambdaG3 polymorphisms and MS was found, only a non significant tendency to reduced PlambdaG3 allele sharing among dizygotic non concordant twin pairs was observed. However one Vbeta11, 25 kb allele and a haplotype defined by Vbeta11 and Cbeta alleles showed a correlation with MS susceptibility of borderline significance. These observations are in favor of a slight effect of a genetic factor in the TCRbeta gene region in MS genetic susceptibility whereas this is not the case for Vgamma genes.
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页码:67 / 73
页数:7
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共 35 条
  • [31] Oksenberg J.R., Sherritt M., Begovitch A.B., Erlich H.A., Bernard C., Cavalli-Sforza L.L., Steinman L., T-cell receptor V alpha and C alpha alleles associated with multiple sclerosis and myasthenia gravis, Proc Natl Acad Sci USA, 86, pp. 988-992, (1989)
  • [32] Charmley P., Concannon P., Gatty R.A., T-cell receptor β chain DNA polymorphism frequencies in healthy HLA-DR homozygotes, Tissue Antigens, 35, pp. 157-164, (1990)
  • [33] Fugger L., Sandberg-Wollheim M., Morling N., Ryder L.P., Svejgaard A., The germline repertoire of T-cell receptor β chain genes in patients with relapsing/remitting multiple sclerosis or optic neuritis, Immunogenetics, 31, pp. 278-280, (1990)
  • [34] Lynch S.G., Rose J.W., Peatjan J.H., Discordance of T cell receptor β chain genes in familial multiple sclerosis, Annal Neurol, 30, pp. 402-410, (1989)
  • [35] Sherritt M.A., Oksenberg J.R., Kerlero de Robo N., Bernard C.C., Influence of HLA-DR2, HLA-DPw4 and T-cell receptor chain genes on the susceptibility to multiple sclerosis, International Immunol, 4, pp. 177-181, (1992)