Novel association in chromosome 4q27 region with rheumatoid arthritis and confirmation of type 1 diabetes point to a general risk locus for autoimmune diseases.
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Publication year
2007Source
American Journal of Human Genetics, 81, 6, (2007), pp. 1284-8ISSN
Publication type
Article / Letter to editor
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Organization
Human Genetics
Rheumatology
Journal title
American Journal of Human Genetics
Volume
vol. 81
Issue
iss. 6
Page start
p. 1284
Page end
p. 8
Subject
DCN 1: Perception and Action; DCN 2: Functional Neurogenomics; IGMD 3: Genomic disorders and inherited multi-system disorders; N4i 1: Pathogenesis and modulation of inflammation; N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 1: Immunity, infection and tissue repair; NCMLS 1: Infection and autoimmunity; NCMLS 6: Genetics and epigenetic pathways of disease; UMCN 3.2: Cognitive neurosciences; UMCN 4.2: Chronic inflammation and autoimmunity; UMCN 5.1: Genetic defects of metabolismAbstract
Recently, association of celiac disease with common single-nucleotide polymorphism (SNP) variants in an extensive linkage-disequilibrium block of 480 kb containing the KIAA1109, Tenr, IL2, and IL21 genes has been demonstrated in three independent populations (rs6822844P combined=1.3 x 10(-14)). The KIAA1109/Tenr/IL2/IL21 block corresponds to the Idd3 locus in the nonobese diabetic mouse model of type 1 diabetes (T1D). This block was recently found to be associated with T1D in a genomewide association study, although this finding lacks unequivocal confirmation. We therefore aimed to investigate whether the KIAA1109/Tenr/IL2/IL21 region is involved in susceptibility to multiple autoimmune diseases. We tested SNP rs6822844 for association with disease in 350 T1D-affected and 1,047 rheumatoid arthritis (RA)-affected Dutch patients and in 929 controls. We replicated the association with T1D (P=.0006; OR 0.64 [95% CI 0.50-0.83]), and revealed a similar novel association with RA (P=.0002; OR 0.72 [95% CI 0.61-0.86]). Our results replicate and extend the association found in the KIAA1109/Tenr/IL2/IL21 gene region with autoimmune diseases, implying that this locus is a general risk factor for multiple autoimmune diseases.
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- Faculty of Medical Sciences [90373]
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