Novel Association in Chromosome 4q27 Region with Rheumatoid Arthritis and Confirmation of Type 1 Diabetes Point to a General Risk Locus for Autoimmune Diseases
Copyright policy )Novel Association in Chromosome 4q27 Region with Rheumatoid Arthritis and Confirmation of Type 1 Diabetes Point to a General Risk Locus for Autoimmune Diseases
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.
- Utrecht University Netherlands
- University Medical Center Utrecht Netherlands
- Radboud University Nijmegen Netherlands
- Radboud University Nijmegen Medical Centre Netherlands
- Queen Mary University of London United Kingdom
DCN 1: Perception and Action, UMCN 4.2: Chronic inflammation and autoimmunity, Genotype, NCMLS 1: Immunity, infection and tissue repair, DCN 2: Functional Neurogenomics, N4i 1: Pathogenesis and modulation of inflammation, SUSCEPTIBILITY, NCMLS 6: Genetics and epigenetic pathways of disease, INTERLEUKIN-21, Polymorphism, Single Nucleotide, UMCN 5.1: Genetic defects of metabolism, Autoimmune Diseases, Arthritis, Rheumatoid, IGMD 3: Genomic disorders and inherited multi-system disorders, SDG 3 - Good Health and Well-being, Risk Factors, IL-21, Genetics, Humans, Genetics(clinical), Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, UMCN 3.2: Cognitive neurosciences, MODULATOR, NCMLS 1: Infection and autoimmunity, CELIAC-DISEASE, Chromosome Mapping, PTPN22, Celiac Disease, N4i 4: Auto-immunity, transplantation and immunotherapy, DIFFERENTIATION, Diabetes Mellitus, Type 1, Chromosomes, Human, Pair 4
DCN 1: Perception and Action, UMCN 4.2: Chronic inflammation and autoimmunity, Genotype, NCMLS 1: Immunity, infection and tissue repair, DCN 2: Functional Neurogenomics, N4i 1: Pathogenesis and modulation of inflammation, SUSCEPTIBILITY, NCMLS 6: Genetics and epigenetic pathways of disease, INTERLEUKIN-21, Polymorphism, Single Nucleotide, UMCN 5.1: Genetic defects of metabolism, Autoimmune Diseases, Arthritis, Rheumatoid, IGMD 3: Genomic disorders and inherited multi-system disorders, SDG 3 - Good Health and Well-being, Risk Factors, IL-21, Genetics, Humans, Genetics(clinical), Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, UMCN 3.2: Cognitive neurosciences, MODULATOR, NCMLS 1: Infection and autoimmunity, CELIAC-DISEASE, Chromosome Mapping, PTPN22, Celiac Disease, N4i 4: Auto-immunity, transplantation and immunotherapy, DIFFERENTIATION, Diabetes Mellitus, Type 1, Chromosomes, Human, Pair 4
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