CTLA4 is associated with susceptibility to multiple sclerosis

被引:66
作者
Kantarci, OH
Hebrink, DD
Achenbach, SJ
Atkinson, EJ
Waliszewska, A
Buckle, G
McMurray, CT
de Andrade, M
Hafler, DA
Weinshenker, BG
机构
[1] Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55905 USA
[3] Harvard Univ, Brigham & Womens Hosp, Inst Med, Ctr Neurol Dis, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
[5] Mayo Clin & Mayo Fdn, Dept Pharmacol, Rochester, MN 55905 USA
[6] Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA
[7] Mayo Clin & Mayo Fdn, Mol NeurosciProgram, Rochester, MN 55905 USA
关键词
multiple sclerosis; CTLA-4; polymorphism; susceptibility; prognosis; severity;
D O I
10.1016/S0165-5728(02)00395-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We comprehensively screened CTLA4 for novel genetic variations in patients with MS. We studied genetic variations by association methods in a population-based sample of 122 sporadic patients with MS and 244 age-, gender- and ethnicity-matched controls, and by linkage and family-based association methods in 395 individuals from 59 American multiplex pedigrees with 141 affected individuals. Being homozygous for AT(8) (common) allele of the 3'(514) microsatellite (OR: 1.69; CI: 0.99-2.86) and for the common 5'(318)*C/E1(49)*A/ 3'(514*AT(8) haplotype (OR: 1.96; CI: 1.13-3.39) was associated with increased susceptibility to MS in Olmsted County. The genotype frequencies of other individual polymorphisms were not significantly different between cases and controls. A pooled analysis of association studies revealed an odds ratio of 1.28 (95% CI: 1.01-1.63; p=0.043) for 5'(-318)*C homozygotes and 1.28 (95% CI: 1.08-1.51; p=0.005) for the 3'(514)*AT(8) allele. We did not detect linkage with MS susceptibility in multiplex families. We did not find a strong association with age at onset, disease course or severity. CTLA-4 is associated with susceptibility to MS. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:133 / 141
页数:9
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