title: Genetic analysis of the CD28/CTLA4/ICOS (CELIAC3) region in coeliac disease.
abstract: In order to extend our previous findings of genetic linkage to the CD28/CTLA4/ICOS region on chromosome 2q33 (CELIAC3) in coeliac disease (CD), we have investigated 22 genetic markers in 325 Norwegian/Swedish multiplex and simplex CD families. We found both linkage and association with several markers, primarily in the multiplex material. We observed strong linkage disequilibrium (LD) between SNPs (Single Nucleotide Polymorphisms) within an LD block delimited by MH30 and D2S72. A haplotype of this region marked by the alleles -1147*T: + 49*A:CT60*G:CT61*A was significantly associated with CD, suggesting that one or more polymorphisms of this haplotype, possibly -1147*T, are involved in CD susceptibility. The CT60 SNP, a polymorphism found to be most strongly associated with some other immune-mediated diseases, was not associated with CD, as this SNP was part of both associated and non-associated haplotypes. Moreover, our results suggest that CELIAC3 harbours several independent loci contributing to CD susceptibility.
authors.affiliation: Institute of Immunology, Rikshopitalet University Hospital, University of Oslo, Norway. s.s.amundsen@labmed.uio.no
authors.forename: S S
authors.initials: SS
authors.lastname: Amundsen
authors.forename: A T
authors.initials: AT
authors.lastname: Naluai
authors.forename: H
authors.initials: H
authors.lastname: Ascher
authors.forename: J
authors.initials: J
authors.lastname: Ek
authors.forename: A H
authors.initials: AH
authors.lastname: Gudjónsdóttir
authors.forename: J
authors.initials: J
authors.lastname: Wahlström
authors.forename: B A
authors.initials: BA
authors.lastname: Lie
authors.forename: L M
authors.initials: LM
authors.lastname: Sollid
mesh_terms: D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D018106:CD28 Antigens / Q000235:genetics*; D060908:CTLA-4 Antigen; D002446:Celiac Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein