TY - JOUR
T1 - CD95 polymorphisms are associated with susceptibility to MS in women
T2 - A population-based study of CD95 and CD95L in MS
AU - Kantarci, Orhun H.
AU - Hebrink, David D.
AU - Achenbach, Sara J.
AU - Atkinson, Elizabeth J.
AU - De Andrade, Mariza
AU - McMurray, Cynthia T.
AU - Weinshenker, Brian G.
PY - 2004/1
Y1 - 2004/1
N2 - 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.
AB - 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.
KW - CD95
KW - CD95L
KW - Gender
KW - Multiple sclerosis
KW - Polymorphism
KW - Susceptibility
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U2 - 10.1016/j.jneuroim.2003.10.002
DO - 10.1016/j.jneuroim.2003.10.002
M3 - Article
C2 - 14698859
AN - SCOPUS:0347993160
SN - 0165-5728
VL - 146
SP - 162
EP - 170
JO - Journal of neuroimmunology
JF - Journal of neuroimmunology
IS - 1-2
ER -