Genome-wide association analysis identifies new susceptibility loci for Behcet's disease and epistasis between HLA-B*51 and ERAP1

被引：425

作者：

Kirino, Yohei ^{[1
,2
]}

Bertsias, George ^{[1
,3
]}

Ishigatsubo, Yoshiaki ^{[2
]}

Mizuki, Nobuhisa ^{[4
]}

Tugal-Tutkun, Ilknur ^{[5
]}

Seyahi, Emire ^{[6
]}

Ozyazgan, Yilmaz ^{[7
]}

Sacli, F. Sevgi ^{[6
]}

Erer, Burak ^{[8
]}

Inoko, Hidetoshi ^{[9
]}

Emrence, Zeliha ^{[10
]}

Cakar, Atilla ^{[10
]}

Abaci, Neslihan ^{[10
]}

Ustek, Duran ^{[10
]}

Satorius, Colleen ^{[1
]}

Ueda, Atsuhisa ^{[2
]}

Takeno, Mitsuhiro ^{[2
]}

Kim, Yoonhee ^{[11
]}

Wood, Geryl M. ^{[1
]}

Ombrello, Michael J. ^{[1
]}

Meguro, Akira ^{[4
]}

Gul, Ahmet ^{[8
]}

Remmers, Elaine F. ^{[1
]}

Kastner, Daniel L. ^{[1
]}

机构：

[1] NHGRI, Inflammatory Dis Sect, Med Genet Branch, US NIH, Bethesda, MD 20892 USA

[2] Yokohama City Univ, Grad Sch Med, Dept Internal Med & Clin Immunol, Yokohama, Kanagawa 232, Japan

[3] Univ Crete, Fac Med, Iraklion, Greece

[4] Yokohama City Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Yokohama, Kanagawa 232, Japan

[5] Istanbul Univ, Dept Ophthalmol, Istanbul Fac Med, Istanbul, Turkey

[6] Istanbul Univ, Dept Internal Med, Cerrahpasa Fac Med, Div Rheumatol, Istanbul, Turkey

[7] Istanbul Univ, Dept Ophthalmol, Cerrahpasa Fac Med, Istanbul, Turkey

[8] Istanbul Univ, Dept Internal Med, Div Rheumatol, Istanbul Fac Med, Istanbul, Turkey

[9] Tokai Univ, Sch Med, Dept Mol Life Sci, Div Mol Med Sci & Mol Med, Isehara, Kanagawa 25911, Japan

[10] Istanbul Univ, Dept Genet, Inst Expt Med, Istanbul, Turkey

[11] NHGRI, Genometr Sect, Inherited Dis Res Branch, US NIH, Baltimore, MD USA

来源：

NATURE GENETICS | 2013年 / 45卷 / 02期

基金：

美国国家卫生研究院;

关键词：

MHC CLASS-I; ANKYLOSING-SPONDYLITIS; METAANALYSIS; PSORIASIS; NKG2D; RISK; IL23R-IL12RB2; ARTHRITIS; NUMBER; IL10;

D O I：

10.1038/ng.2520

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：202 / 207

页数：6

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