CTLA4 is associated with susceptibility to multiple sclerosis

Orhun H. Kantarci, David D. Hebrink, Sara J. Achenbach, Elizabeth J. Atkinson, Alicja Waliszewska, Guy Buckle, Cynthia T. McMurray, Mariza De Andrade, David A. Hafler, Brian G. Weinshenker

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

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 AT8 (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*AT8 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)*AT8 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.

Original languageEnglish (US)
Pages (from-to)133-141
Number of pages9
JournalJournal of neuroimmunology
Volume134
Issue number1-2
DOIs
StatePublished - Jan 1 2003

Keywords

  • CTLA-4
  • Multiple sclerosis
  • Polymorphism
  • Prognosis
  • Severity
  • Susceptibility

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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  • Cite this

    Kantarci, O. H., Hebrink, D. D., Achenbach, S. J., Atkinson, E. J., Waliszewska, A., Buckle, G., McMurray, C. T., De Andrade, M., Hafler, D. A., & Weinshenker, B. G. (2003). CTLA4 is associated with susceptibility to multiple sclerosis. Journal of neuroimmunology, 134(1-2), 133-141. https://doi.org/10.1016/S0165-5728(02)00395-8