1. CTLA4 is associated with susceptibility to multiple sclerosis.
- Author
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Kantarci OH, Hebrink DD, Achenbach SJ, Atkinson EJ, Waliszewska A, Buckle G, McMurray CT, de Andrade M, Hafler DA, and Weinshenker BG
- Subjects
- Abatacept, Age of Onset, Alternative Splicing genetics, Antigens, CD, Antigens, Differentiation immunology, Boston, CTLA-4 Antigen, DNA Mutational Analysis, Disease Progression, Exons genetics, Female, Genetic Linkage genetics, Genetic Testing, Genotype, Haplotypes genetics, Humans, Male, Microsatellite Repeats genetics, Minnesota, Multiple Sclerosis immunology, Antigens, Differentiation genetics, Genetic Predisposition to Disease genetics, Genetic Variation genetics, Immunoconjugates, Multiple Sclerosis genetics, Polymorphism, Genetic genetics
- 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.
- Published
- 2003
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