Genome-wide Association Study Identifies TNFSF15 and POU2AF1 as Susceptibility Loci for Primary Biliary Cirrhosis in the Japanese Population

被引：222

作者：

Nakamura, Minoru ^{[1
,2
,3
,4
]}

Nishida, Nao ^{[5
,6
]}

Kawashima, Minae ^{[5
]}

Aiba, Yoshihiro ^{[1
,2
]}

Tanaka, Atsushi ^{[7
]}

Yasunami, Michio ^{[8
]}

Nakamura, Hitomi ^{[1
,2
]}

Komori, Atsumasai ^{[1
,2
]}

Nakamuta, Makoto ^{[3
]}

Zeniya, Mikio ^{[9
]}

Hashimoto, Etsuko ^{[10
]}

Ohira, Hiromasa ^{[11
]}

Yamamoto, Kazuhide ^{[12
]}

Onji, Morikazu ^{[13
]}

Kaneko, Shuichi ^{[14
]}

Honda, Masao ^{[14
]}

Yamagiwa, Satoshi ^{[15
]}

Nakao, Kazuhiko ^{[16
]}

Ichida, Takafumi ^{[17
]}

Takikawa, Hajime ^{[7
]}

Seike, Masataka ^{[18
]}

Umemura, Takeji ^{[19
]}

Ueno, Yoshiyuki ^{[20
]}

Sakisaka, Shotaro ^{[21
]}

Kikuchi, Kentaro ^{[22
]}

Ebinuma, Hirotoshi ^{[23
]}

Yamashiki, Noriyo ^{[24
]}

Tamura, Sumito ^{[25
,26
]}

Sugawara, Yasuhiko ^{[25
,26
]}

Mori, Akira ^{[27
]}

Yagi, Shintaro ^{[27
]}

Shirabe, Ken

Taketomi, Akinobu

Arai, Kuniaki ^{[14
]}

Monoe, Kyoko ^{[11
]}

Ichikawa, Tatsuki ^{[16
]}

Taniai, Makiko ^{[10
]}

Miyake, Yasuhiro ^{[12
]}

Kumagi, Teru ^{[13
]}

Abe, Masanori ^{[13
]}

Yoshizawa, Kaname ^{[19
]}

Joshita, Satoru ^{[19
]}

Shimoda, Shinji ^{[28
]}

Honda, Koichi ^{[18
]}

Takahashi, Hiroki ^{[9
]}

Hirano, Katsuji ^{[17
]}

Takeyama, Yasuaki ^{[21
]}

Harada, Kenichi ^{[29
]}

Migita, Kiyoshi ^{[1
,2
]}

Ito, Masahiro ^{[1
,2
]}

机构：

[1] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki Med Ctr, Clin Res Ctr,NHO, Omura, Nagasaki 8568562, Japan

[2] Nagasaki Univ, Grad Sch Biomed Sci, Dept Hepatol, Omura, Nagasaki 8568562, Japan

[3] NHO Nagasaki Med Ctr, Clin Res Ctr, Headquaters Primary Biliary Cirrhosis Res NHO Stu, Omura, Nagasaki 8568562, Japan

[4] Nagasaki Univ, Grad Sch Biomed Sci, Headquaters Working Grp Gp210,Dept Hepatol, Intractable Liver Dis Res Project Team,Minist Hlt, Omura, Nagasaki 8568562, Japan

[5] Univ Tokyo, Grad Sch Med, Dept Human Genet, Tokyo 1130033, Japan

[6] Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol, Ichikawa 2728516, Japan

[7] Teikyo Univ, Sch Med, Dept Med, Tokyo 1738605, Japan

[8] Nagasaki Univ, Inst Trop Med, Dept Clin Med, Nagasaki 8528523, Japan

[9] Tokyo Jikei Univ, Sch Med, Dept Gastroenterol & Hepatol, Tokyo 1058461, Japan

[10] Tokyo Womens Med Univ, Dept Med & Gastroenterol, Tokyo 1628666, Japan

[11] Fukushima Med Univ, Dept Gastroenterol & Rheumat Dis, Fukushima 9601295, Japan

[12] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gastroenterol & Hepatol, Okayama 7008558, Japan

[13] Ehime Univ, Grad Sch Med, Dept Gastroenterol & Med, Matsuyama, Ehime 7910295, Japan

[14] Kanazawa Univ, Grad Sch Med, Dept Gastroenterol, Kanazawa, Ishikawa 9200942, Japan

[15] Niigata Univ, Grad Sch Med & Dent Sci, Div Gastroenterol & Hepatol, Niigata 9518510, Japan

[16] Nagasaki Univ, Grad Sch Biomed Sci, Dept Gastroenterol & Hepatol, Nagaski 8528501, Japan

[17] Juntendo Univ, Shizuoka Hosp, Dept Gastroenterol & Hepatol, Shizuoka 4102295, Japan

[18] Oita Univ, Fac Med, Dept Internal Med 1, Oita 8795593, Japan

[19] Shinshu Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Matsumoto, Nagano 3908621, Japan

[20] Tohoku Univ, Grad Sch Med, Div Gastroenterol, Sendai, Miyagi 9808575, Japan

[21] Fukuoka Univ, Sch Med, Dept Gastroenterol & Med, Fukuoka 8140180, Japan

[22] Teikyo Univ, Mizonokuchi Hosp, Dept Internal Med, Kawasaki, Kanagawa 2138507, Japan

[23] Keio Grad Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo 1608582, Japan

[24] Univ Tokyo, Organ Transplantat Serv, Tokyo 1138655, Japan

[25] Univ Tokyo, Grad Sch Med, Dept Surg, Hepatobiliary & Pancreat Surg Div, Tokyo 1138655, Japan

[26] Univ Tokyo, Grad Sch Med, Dept Surg, Artificial Organ & Transplantat Div, Tokyo 1138655, Japan

[27] Kyoto Univ, Grad Sch Med, Dept Surg, Div Hepatopancreatobiliary Surg & Transplantat, Kyoto 6068507, Japan

[28] Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosyst Sci, Fukuoka 8128582, Japan

[29] Kanazawa Univ, Grad Sch Med, Dept Human Pathol, Kanazawa, Ishikawa 9200942, Japan

[30] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Digest & Lifestyle Related Dis, Kagoshima 8908520, Japan

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2012年 / 91卷 / 04期

基金：

日本学术振兴会;

关键词：

INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; COACTIVATOR OBF-1; SNP ARRAY; SPI-B; VARIANTS; POLYMORPHISMS; GENERATION; CELLS; INDIVIDUALS;

D O I：

10.1016/j.ajhg.2012.08.010

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

For the identification of susceptibility loci for primary binary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 x 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 x 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 x 10(-8), 3.66 x 10(-9), and 3.04 x 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 x 10(-6) and 1.42 x 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.

引用

页码：721 / 728

页数：8

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