title: A two-stage study on multiple sclerosis susceptibility and chromosome 2q33.
abstract: We have performed a two-stage study to analyse the association of polymorphism on chromosome 2q33 with multiple sclerosis (MS). In all, 17 markers were analysed in stage-1 in 134 Finnish MS families and the observed associations were tested in stage-2 in 186 MS families. We did not find previously reported allelic or haplotype associations with CTLA4. We obtained a weak signal of two distinct predisposing genes, one proximal the other distal of CTLA4. The putative proximal gene was associated with the marker rs3977 in families lacking HLA-DR2 (P=0.02 and 0.02) and the other distal gene was associated with D2S1271 in families from a high-risk region in western Finland (P=0.02 and 0.01). Based on the >3 cM distance and the lack of linkage disequilibrium between these loci, we conclude that the two association signals are independent. Our results provide preliminary evidence for two distinct MS susceptibility genes on 2q33 outside of CTLA4.
authors.affiliation: Department of Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki University Central Hospital, Haartmaninkatu 4, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Bonetti
authors.forename: K
authors.initials: K
authors.lastname: Reunanen
authors.forename: S
authors.initials: S
authors.lastname: Finnilä
authors.forename: K
authors.initials: K
authors.lastname: Koivisto
authors.forename: J
authors.initials: J
authors.lastname: Wikström
authors.forename: M-L
authors.initials: ML
authors.lastname: Sumelahti
authors.forename: T
authors.initials: T
authors.lastname: Pirttilä
authors.forename: I
authors.initials: I
authors.lastname: Elovaara
authors.forename: M
authors.initials: M
authors.lastname: Reunanen
authors.forename: J
authors.initials: J
authors.lastname: Saarela
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
authors.forename: T
authors.initials: T
authors.lastname: Rantamäki
authors.forename: P J
authors.initials: PJ
authors.lastname: Tienari
mesh_terms: D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D060908:CTLA-4 Antigen; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D005387:Finland; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers