Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease.
Behçet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behçet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behçet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production.
Remmers
Elaine F
EF
National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA. remmerse@mail.nih.gov
Cosan
Fulya
F
Kirino
Yohei
Y
Ombrello
Michael J
MJ
Abaci
Neslihan
N
Satorius
Colleen
C
Le
Julie M
JM
Yang
Barbara
B
Korman
Benjamin D
BD
Cakiris
Aris
A
Aglar
Oznur
O
Emrence
Zeliha
Z
Azakli
Hulya
H
Ustek
Duran
D
Tugal-Tutkun
Ilknur
I
Akman-Demir
Gulsen
G
Chen
Wei
W
Amos
Christopher I
CI
Dizon
Michael B
MB
Kose
Afet Akdag
AA
Azizlerli
Gulsevim
G
Erer
Burak
B
Brand
Oliver J
OJ
Kaklamani
Virginia G
VG
Kaklamanis
Phaedon
P
Ben-Chetrit
Eldad
E
Stanford
Miles
M
Fortune
Farida
F
Ghabra
Marwen
M
Ollier
William E R
WE
Cho
Young-Hun
YH
Bang
Dongsik
D
O'Shea
John
J
Wallace
Graham R
GR
Gadina
Massimo
M
Kastner
Daniel L
DL
Gül
Ahmet
A
D000483:Alleles; D001208:Asia; D001528:Behcet Syndrome / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005060:Europe; D005805:Genes, MHC Class I / Q000235:genetics*; D055106:Genome-Wide Association Study; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D008877:Middle East; D020641:Polymorphism, Single Nucleotide; D014421:Turkey
D015235:HLA-B Antigens; D016753:Interleukin-10