A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population

被引：226

作者：

Asano, Kouichi ^{[1
,2
,3
]}

Matsushita, Tomonaga ^{[1
,2
]}

Umeno, Junji ^{[1
,2
]}

Hosono, Naoya ^{[1
]}

Takahashi, Atsushi ^{[4
]}

Kawaguchi, Takahisa ^{[5
]}

Matsumoto, Takayuki ^{[2
]}

Matsui, Toshiyuki ^{[6
]}

Kakuta, Yoichi ^{[7
]}

Kinouchi, Yoshitaka ^{[7
]}

Shimosegawa, Tooru ^{[7
]}

Hosokawa, Masayo ^{[8
]}

Arimura, Yoshiaki ^{[8
]}

Shinomura, Yasuhisa ^{[8
]}

Kiyohara, Yutaka ^{[3
]}

Tsunoda, Tatsuhiko ^{[5
]}

Kamatani, Naoyuki ^{[4
]}

Iida, Mitsuo ^{[2
]}

Nakamura, Yusuke ^{[9
]}

Kubo, Michiaki ^{[1
,2
,3
]}

机构：

[1] RIKEN, Yokohama Inst, Ctr Genom Med, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[2] Kyushu Univ, Dept Med & Clin Sci, Grad Sch Med Sci, Fukuoka 812, Japan

[3] Kyushu Univ, Grad Sch Med Sci, Dept Environm Med, Fukuoka 812, Japan

[4] RIKEN, Yokohama Inst, Ctr Genom Med, Lab Stat Anal, Yokohama, Kanagawa, Japan

[5] RIKEN, Yokohama Inst, Ctr Genom Med, Lab Med Informat, Yokohama, Kanagawa, Japan

[6] Fukuoka Univ, Chikushi Hosp, Dept Gastroenterol, Fukuoka 81401, Japan

[7] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Sendai, Miyagi 980, Japan

[8] Sapporo Med Univ, Sch Med, Dept Internal Med 1, Sapporo, Hokkaido, Japan

[9] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan

来源：

NATURE GENETICS | 2009年 / 41卷 / 12期

关键词：

INFLAMMATORY-BOWEL-DISEASE; CONGENITAL CHLORIDE DIARRHEA; COPY NUMBER VARIATION; CROHNS-DISEASE; RHEUMATOID-ARTHRITIS; RISK-FACTORS; VARIANTS; GENE; AUTOIMMUNITY; DEFINES;

D O I：

10.1038/ng.482

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Ulcerative colitis is one of the principal forms of inflammatory bowel disease with complex manifestations. Although previous studies have indicated that there is a genetic contribution to the pathogenesis of ulcerative colitis, the genes influencing susceptibility to the disease have not been fully determined. To identify genetic factors conferring risk of ulcerative colitis, here we conducted a two-stage genome-wide association study and subsequent replication study using 1,384 Japanese individuals with ulcerative colitis and 3,057 control subjects. In addition to the expected strong association with the major histocompatibility complex (MHC) region, we identified three new susceptibility loci: the immunoglobulin receptor gene FCGR2A (rs1801274, P = 1.56 x 10(-12)), a locus on chromosome 13q12 (rs17085007, P = 6.64 x 10(-8)) and the glycoprotein gene SLC26A3 (rs2108225, P = 9.50 x 10(-8)). rs1801274 is a nonsynonymous SNP of FCGR2A that is reported to have a critical effect on receptor binding affinity for IgG and to be associated with other autoimmune diseases. Our findings provide insight into the molecular pathogenesis of ulcerative colitis.

引用

页码：1325 / U92

页数：7

共 33 条

[11] Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis [J].

Franke, Andre ;

Balschun, Tobias ;

Karlsen, Tom H. ;

Hedderich, Juergen ;

May, Sandra ;

Lu, Tim ;

Schuldt, Doerthe ;

Nikolaus, Susanna ;

Rosenstiel, Philip ;

Krawczak, Michael ;

Schreiber, Stefan .

NATURE GENETICS, 2008, 40 (06) :713-715

[12] HLA-DRB1-ASTERISK-1502 ALLELE, SUBTYPE OF DR15, IS ASSOCIATED WITH SUSCEPTIBILITY TO ULCERATIVE-COLITIS AND ITS PROGRESSION [J].

FUTAMI, S ;

AOYAMA, N ;

HONSAKO, Y ;

TAMURA, T ;

MORIMOTO, S ;

NAKASHIMA, T ;

OHMOTO, A ;

OKANO, H ;

MIYAMOTO, M ;

INABA, H ;

NARUSE, T ;

NOSE, Y ;

KASUGA, M .

DIGESTIVE DISEASES AND SCIENCES, 1995, 40 (04) :814-818

[13] Mechanism underlying inhibition of intestinal apical Cl-/OH- exchange following infection with enteropathogenic E-coli [J].

Gill, Ravinder K. ;

Borthakur, Alip ;

Hodges, Kim ;

Turner, Jerrold R. ;

Clayburgh, Daniel R. ;

Saksena, Seema ;

Zaheer, Ayesha ;

Ramaswamy, Krishnamurthy ;

Hecht, Gail ;

Dudeja, Pradeep K. .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (02) :428-437

[14] Family and twin studies in inflammatory bowel disease [J].

Halme, Leena ;

Paavola-Sakki, Paulina ;

Turunen, Ulla ;

Lappalainen, Maarit ;

Farkkila, Martti ;

Kontula, Kimmo .

WORLD JOURNAL OF GASTROENTEROLOGY, 2006, 12 (23) :3668-3672

[15] A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 [J].

Hampe, Jochen ;

Franke, Andre ;

Rosenstiel, Philip ;

Till, Andreas ;

Teuber, Markus ;

Huse, Klaus ;

Albrecht, Mario ;

Mayr, Gabriele ;

De La Vega, Francisco M. ;

Briggs, Jason ;

Guenther, Simone ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Haesler, Robert ;

Sipos, Bence ;

Foelsch, Ulrich R. ;

Lengauer, Thomas ;

Platzer, Matthias ;

Mathew, Christopher G. ;

Krawczak, Michael ;

Schreiber, Stefan .

NATURE GENETICS, 2007, 39 (02) :207-211

[16] Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci [J].

Harley, John B. ;

Alarcon-Riquelme, Marta E. ;

Criswell, Lindsey A. ;

Jacob, Chaim O. ;

Kimberly, Robert P. ;

Moser, Kathy L. ;

Tsao, Betty P. ;

Vyse, Timothy J. ;

Langefeld, Carl D. .

NATURE GENETICS, 2008, 40 (02) :204-210

[17] Mutations of the Down-regulated in adenoma (DRA) gene cause congenital chloride diarrhoea [J].

Hoglund, P ;

Haila, S ;

Socha, J ;

Tomaszewski, L ;

SaarialhoKere, U ;

KarjalainenLindsberg, ML ;

Airola, K ;

Holmberg, C ;

delaChapelle, A ;

Kere, J .

NATURE GENETICS, 1996, 14 (03) :316-319

[18] Multiplex PCR-based real-time invader assay (mPCR-RETINA): A novel SNP-based method for detecting allellic asymmetries within copy number variation regions [J].

Hosono, Naoya ;

Kubo, Michiaki ;

Tsuchiya, Yumiko ;

Sato, Hiroko ;

Kitamoto, Takuya ;

Saito, Susumu ;

Ohnishi, Yozo ;

Nakamura, Yusuke .

HUMAN MUTATION, 2008, 29 (01) :182-189

[19] Ten-year prognosis of stroke and risk factors for death in a Japanese community - The Hisayama Study [J].

Kiyohara, Y ;

Kubo, M ;

Kato, I ;

Tanizaki, Y ;

Tanaka, K ;

Okubo, K ;

Nakamura, H ;

Iida, M .

STROKE, 2003, 34 (10) :2343-2347

[20] CLASSIFICATION OF INFLAMMATORY BOWEL-DISEASE [J].

LENNARDJONES, JE .

SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1989, 24 :2-6

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