title: Novel association in chromosome 4q27 region with rheumatoid arthritis and confirmation of type 1 diabetes point to a general risk locus for autoimmune diseases.
abstract: 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.
authors.affiliation: Complex Genetics Section, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zhernakova
authors.forename: Behrooz Z
authors.initials: BZ
authors.lastname: Alizadeh
authors.forename: Marianna
authors.initials: M
authors.lastname: Bevova
authors.forename: Miek A
authors.initials: MA
authors.lastname: van Leeuwen
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Coenen
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Lude
authors.initials: L
authors.lastname: Franke
authors.forename: Marcel D
authors.initials: MD
authors.lastname: Posthumus
authors.forename: David A
authors.initials: DA
authors.lastname: van Heel
authors.forename: Gerrit
authors.initials: G
authors.lastname: van der Steege
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
authors.forename: Bart O
authors.initials: BO
authors.lastname: Roep
authors.forename: Bobby P C
authors.initials: BP
authors.lastname: Koeleman
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics*; D002446:Celiac Disease / Q000235:genetics; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors