Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behcet's disease susceptibility
Tarih
2017Yazar
REMMERS, Elaine F.
TAKEUCHI, Masaki
MIZUKI, Nobuhisa
MEGURO, Akira
OMBRELLO, Michael J.
KIRINO, Yohei
SATORIUS, Colleen
GADINA, Massimo
Oliveira, Sofia A.
KASTNER, Daniel L.
Gül, Ahmet
Seyahi, Emire
LE, Julie
BLAKE, Mary
ERER, Burak
KAWAGOE, Tatsukata
Ustek, Duran
Tugal-Tutkun, Ilknur
Ozyazgan, Yilmaz
Sousa, Ines
DAVATCHI, Fereydoun
Francisco, Vania
SHAHRAM, Farhad
ABDOLLAHI, Bahar Sadeghi
NADJI, Abdolhadi
SHAFIEE, Niloofar Mojarad
GHADERIBARMI, Fahmida
Ohno, Shigeaki
UEDA, Atsuhisa
ISHIGATSUBO, Yoshiaki
Üst veri
Tüm öğe kaydını gösterÖzet
We analyzed 1,900 Turkish Behcet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three new risk loci, IL1A-IL18, IRF8, and CEBPB-PTPN1, with genomewide significance (P < 5 x 10(-8)) by direct genotyping and ADO-EGR2 by imputation. We replicated the ADO-EGR2, IRF8, and CEBPB-PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO-EGR2 and IRF8, and meta analysis additionally identified R1PK2 and LACC1. The disease associated allele of rs4402765, the lead marker at 11.1A-ILIB, was associated with both decreased IL-1 alpha and increased IL-1 beta production. ABO non-secretor genotypes for two ancestry specific FUT2 SNPs showed strong disease association (P = 5.89 x 10(-15)). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behcet's disease susceptibility.
Koleksiyonlar
- Makale [92796]