Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behcet's disease

被引：537

作者：

Remmers, Elaine F. ^{[1
]}

Cosan, Fulya ^{[2
]}

Kirino, Yohei ^{[1
]}

Ombrello, Michael J. ^{[1
]}

Abaci, Neslihan ^{[3
]}

Satorius, Colleen ^{[1
]}

Le, Julie M. ^{[1
]}

Yang, Barbara ^{[4
]}

Korman, Benjamin D. ^{[1
]}

Cakiris, Aris ^{[3
]}

Aglar, Oznur ^{[3
]}

Emrence, Zeliha ^{[3
]}

Azakli, Hulya ^{[3
]}

Ustek, Duran ^{[3
]}

Tugal-Tutkun, Ilknur ^{[5
]}

Akman-Demir, Gulsen ^{[6
]}

Chen, Wei ^{[7
]}

Amos, Christopher I. ^{[7
]}

Dizon, Michael B. ^{[4
]}

Kose, Afet Akdag ^{[8
]}

Azizlerli, Gulsevim ^{[8
]}

Erer, Burak ^{[2
]}

Brand, Oliver J. ^{[9
]}

Kaklamani, Virginia G. ^{[10
]}

Kaklamanis, Phaedon ^{[11
]}

Ben-Chetrit, Eldad ^{[12
]}

Stanford, Miles ^{[13
]}

Fortune, Farida ^{[14
]}

Ghabra, Marwen ^{[15
]}

Ollier, William E. R. ^{[16
]}

Cho, Young-Hun ^{[17
]}

Bang, Dongsik ^{[18
]}

O'Shea, John ^{[19
]}

Wallace, Graham R. ^{[20
]}

Gadina, Massimo ^{[4
]}

Kastner, Daniel L. ^{[1
]}

Gul, Ahmet ^{[2
,3
]}

机构：

[1] NIAMSD, Clin Invest Lab, Bethesda, MD 20892 USA

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

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

[4] NIAMSD, Translat Immunol Sect, Off Sci & Technol, Bethesda, MD 20892 USA

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

[6] Istanbul Univ, Istanbul Fac Med, Dept Neurol, Istanbul, Turkey

[7] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[8] Istanbul Univ, Dept Dermatol, Istanbul Fac Med, Istanbul, Turkey

[9] Univ Birmingham, Sch Clin & Expt Med, Coll Med & Dent Sci, Birmingham, W Midlands, England

[10] Northwestern Univ, Translat Breast Canc Res Div Hematol & Oncol, Chicago, IL 60611 USA

[11] Athens Med Ctr, Dept Rheumatol, Athens, Greece

[12] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel

[13] Kings Coll London, London WC2R 2LS, England

[14] Queen Marys Coll, London, England

[15] Univ Hosp, Damascus, Syria

[16] Univ Manchester, Ctr Integrated Genom Med Res, Sch Immun & Infect, Manchester, Lancs, England

[17] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea

[18] Yonsei Univ, Coll Med, Dept Dermatol, Seoul, South Korea

[19] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA

[20] Univ Birmingham, Acad Unit Ophthalmol, Birmingham, W Midlands, England

来源：

NATURE GENETICS | 2010年 / 42卷 / 08期

基金：

美国国家卫生研究院;

关键词：

INFLAMMATORY-BOWEL-DISEASE; INTERLEUKIN-10; RECEPTOR; LOCI; RISK; GENE; SUSCEPTIBILITY; TRANSCRIPTION; POLYMORPHISM; PROMOTER; COLITIS;

D O I：

10.1038/ng.625

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Behcet'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 Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet'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.

引用

页码：698 / U78

页数：7

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