Genome-wide association analysis identifies new susceptibility loci for Behcet's disease and epistasis between HLA-B*51 and ERAP1
Tarih
2013Yazar
Ueda, Atsuhisa
Kirino, Yohei
Bertsias, George
Ishigatsubo, Yoshiaki
Mizuki, Nobuhisa
Seyahi, Emire
Sacli, F. Sevgi
Erer, Burak
Inoko, Hidetoshi
Satorius, Colleen
Takeno, Mitsuhiro
Kim, Yoonhee
Wood, Geryl M.
Ombrello, Michael J.
Meguro, Akira
Remmers, Elaine F.
Kastner, Daniel L.
Cakar, Atilla
Ustek, Duran
Ozyazgan, Yilmaz
Tugal-Tutkun, Ilknur
Gul, Ahmet
Abaci, Neslihan
Emrence, Zeliha
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Tüm öğe kaydını gösterÖzet
Individuals with Behcet's disease suffer from episodic inflammation often affecting the orogenital mucosa, skin and eyes. To discover new susceptibility loci for Behcet's disease, we performed a genome-wide association study (GWAS) of 779,465 SNPs with imputed genotypes in 1,209 Turkish individuals with Behcet's disease and 1,278 controls. We identified new associations at CCR1, STAT4 and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p.Arg725Gln alterations, recessively conferred disease risk. These findings were replicated in 1,468 independent Turkish and/or 1,352 Japanese samples (combined meta-analysis P < 2 x 10(-9)). We also found evidence for interaction between HLA-B*51 and ERAP1 (P = 9 x 10(-4)). The CCR1 and STAT4 variants were associated with gene expression differences. Three risk loci shared with ankylosing spondylitis and psoriasis (the MHC class I region, ERAP1 and IL23R and the MHC class I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and Behcet's disease.
Koleksiyonlar
- Makale [92796]