CD95 polymorphisms are associated with susceptibility to MS in women: A population-based study of CD95 and CD95L in MS

Orhun H. Kantarci, David D. Hebrink, Sara J. Achenbach, Elizabeth J. Atkinson, Mariza De Andrade, Cynthia T. McMurray, Brian G. Weinshenker

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

CD95/CD95L interaction results in activation-induced apoptosis thereby regulating clonal expansion of T cells outside the thymus. Genetic defects in this system result in autoimmune lymphoproliferation in mice and men. CD95-induced cell death may be defective in MS. We studied the association of CD95 and CD95L polymorphisms with MS in 221 unique patients representing 79% ascertainment in Olmsted County, MN, and 442 gender-, age- and ethnicity-matched controls. Being a homozygote for the G allele of CD95 5′(-670)*A→G SNP (p=0.034; OR: 1.59, 95% CI: 1.06-2.38) and for the C allele of CD95 E7(74)*C→T SNP (p=0.007; OR: 1.73, 95% CI: 1.17-2.56) increased susceptibility to MS exclusively in women. There was strong but incomplete linkage disequilibrium between the two markers (p<0.001; D′=0.546). Homozygosity for 5′(-670)*A or E7(74)*C explained 28% of risk of MS in women but 0% of the risk in men in Olmsted County, MN. Our results agree with the previously published studies and highlight that the association of the polymorphisms is restricted to women with MS. We did not find an association between CD95L and susceptibility to MS nor CD95 or CD95L and age of onset, disease course and disease severity.

Original languageEnglish (US)
Pages (from-to)162-170
Number of pages9
JournalJournal of neuroimmunology
Volume146
Issue number1-2
DOIs
StatePublished - Jan 2004

Keywords

  • CD95
  • CD95L
  • Gender
  • Multiple sclerosis
  • Polymorphism
  • Susceptibility

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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