title: CTLA4 is associated with susceptibility to multiple sclerosis.
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 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.
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: Alicja
authors.initials: A
authors.lastname: Waliszewska
authors.forename: Guy
authors.initials: G
authors.lastname: Buckle
authors.forename: Cynthia T
authors.initials: CT
authors.lastname: McMurray
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: Brian G
authors.initials: BG
authors.lastname: Weinshenker
mesh_terms: D000069594:Abatacept; D017668:Age of Onset; D017398:Alternative Splicing / Q000235:genetics; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000276:immunology; D001900:Boston; D060908:CTLA-4 Antigen; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D018796:Immunoconjugates; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008910:Minnesota; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept