title: CD95 polymorphisms are associated with susceptibility to MS in women. A population-based study of CD95 and CD95L in MS.
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.
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, 200 First Street, SW, Rochester, MN 55905, USA.
authors.forename: Orhun H
authors.initials: OH
authors.lastname: Kantarci
authors.forename: David D
authors.initials: DD
authors.lastname: Hebrink
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Achenbach
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Atkinson
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Cynthia T
authors.initials: CT
authors.lastname: McMurray
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
mesh_terms: D015331:Cohort Studies; D016001:Confidence Intervals; D053222:Fas Ligand Protein; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor