Candidate gene region 2q33 in European families with coeliac disease.
Chromosome region 2q33 harbours a cluster of genes, CTLA-4, CD28, ICOS and closely located PD-1, all related to immune activation and considered as promising candidate genes for susceptibility to coeliac disease (CD). We present here the results of a genetic linkage and association analysis of nine markers located in this gene region in a large combined European material of 796 families with CD from Finland, Sweden, Norway, UK, France and Italy. The joint analysis supports earlier findings that this susceptibility locus, assigned as CELIAC3, merits further studies. Nominally significant linkage to CD was found in 314 families including affected sib pairs. Each of the five populations showed weak associations to several marker alleles, but the analysis revealed, however, no conclusive evidence for a primary functional gene or gene variant present in the total set of families. The results suggest that the CD risk due to 2q33 gene region is complex and may involve more than one susceptibility allele, which possibly differ from other autoimmune diseases.
Department of Tissue Typing and Research Laboratory, Finnish Red Cross Blood Transfusion Service, Helsinki, Finland. p.holopainen@siaf.unizh.ch
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P
Holopainen
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Naluai
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Moodie
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S
Percopo
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I
Coto
F
F
Clot
H
H
Ascher
L
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Sollid
P
P
Ciclitira
L
L
Greco
F
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Clerget-Darpoux
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Partanen
D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D018106:CD28 Antigens / Q000235:genetics*; D060908:CTLA-4 Antigen; D002446:Celiac Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005060:Europe; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D008297:Male; D011110:Polymorphism, Genetic; D061026:Programmed Cell Death 1 Receptor; D044465:White People / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor