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.
Zhernakova
Alexandra
A
Complex Genetics Section, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Alizadeh
Behrooz Z
BZ
Bevova
Marianna
M
van Leeuwen
Miek A
MA
Coenen
Marieke J H
MJ
Franke
Barbara
B
Franke
Lude
L
Posthumus
Marcel D
MD
van Heel
David A
DA
van der Steege
Gerrit
G
Radstake
Timothy R D J
TR
Barrera
Pilar
P
Roep
Bart O
BO
Koeleman
Bobby P C
BP
Wijmenga
Cisca
C
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