Genome-Wide Association Study Identifies HLA-DP as a Susceptibility Gene for Pediatric Asthma in Asian Populations

被引：106

作者：

Noguchi, Emiko ^{[1
]}

Sakamoto, Hiromi ^{[2
]}

Hirota, Tomomitsu ^{[3
]}

Ochiai, Kaori ^{[1
]}

Imoto, Yoshimasa ^{[1
,4
]}

Sakashita, Masafumi ^{[4
]}

Kurosaka, Fumitake ^{[5
]}

Akasawa, Akira ^{[6
]}

Yoshihara, Shigemi ^{[7
]}

Kanno, Noriko ^{[7
]}

Yamada, Yumi ^{[7
]}

Shimojo, Naoki ^{[8
]}

Kohno, Yoichi ^{[8
]}

Suzuki, Yoichi ^{[9
]}

Kang, Mi-Jin ^{[10
]}

Kwon, Ji-Won ^{[10
]}

Hong, Soo-Jong ^{[10
]}

Inoue, Ken ^{[11
]}

Goto, Yu-ichi ^{[11
]}

Yamashita, Fumio ^{[11
,12
]}

Asada, Takashi ^{[12
]}

Hirose, Hiroshi ^{[13
]}

Saito, Ikuo ^{[13
]}

Fujieda, Shigeharu ^{[4
]}

Hizawa, Nobuyuki ^{[14
]}

Sakamoto, Toru ^{[14
]}

Masuko, Hironori ^{[14
]}

Nakamura, Yusuke ^{[3
]}

Nomura, Ichiro ^{[15
]}

Tamari, Mayumi ^{[3
]}

Arinami, Tadao ^{[1
]}

Yoshida, Teruhiko ^{[2
]}

Saito, Hirohisa ^{[15
]}

Matsumoto, Kenji ^{[15
]}

机构：

[1] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Med Genet, Tsukuba, Ibaraki, Japan

[2] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 104, Japan

[3] RIKEN Ctr Genom Med, Lab Resp Dis, Yokohama, Kanagawa, Japan

[4] Univ Fukui, Fac Med Sci, Dept Otorhinolaryngol Head & Neck Surg, Fukui 910, Japan

[5] Kurosaka Pediat & Allergy Clin, Himji, Japan

[6] Tokyo Metropolitan Childrens Med Ctr, Dept Allergy, Tokyo, Japan

[7] Dokkyo Med Univ, Dept Pediat, Mibu, Tochigi, Japan

[8] Chiba Univ, Dept Pediat, Grad Sch Med, Chiba, Japan

[9] Chiba Univ, Dept Publ Hlth, Grad Sch Med, Chiba, Japan

[10] Univ Ulsan, Coll Med, Asan Med Ctr, Childhood Asthma Atopy Ctr,Dept Pediat, Seoul, South Korea

[11] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Retardat & Birth Defect Res, Tokyo, Japan

[12] Univ Tsukuba, Dept Psychiat, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki, Japan

[13] Keio Univ, Ctr Hlth, Tokyo, Japan

[14] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Resp Med, Tsukuba, Ibaraki, Japan

[15] Natl Res Inst Child Hlth & Dev, Dept Allergy & Immunol, Tokyo, Japan

来源：

PLOS GENETICS | 2011年 / 7卷 / 07期

关键词：

ALLERGIC RHINITIS; RISK; ALLELES; PREVALENCE; EXPRESSION; HAPLOTYPES; CONTRIBUTE; VARIANTS; GENOTYPE; CHILDREN;

D O I：

10.1371/journal.pgen.1002170

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Asthma is a complex phenotype influenced by genetic and environmental factors. We conducted a genome-wide association study (GWAS) with 938 Japanese pediatric asthma patients and 2,376 controls. Single-nucleotide polymorphisms (SNPs) showing strong associations (P < 1x10(-8)) in GWAS were further genotyped in an independent Japanese samples (818 cases and 1,032 controls) and in Korean samples (835 cases and 421 controls). SNP rs987870, located between HLA-DPA1 and HLA-DPB1, was consistently associated with pediatric asthma in 3 independent populations (P-combined = 2.3x10(-10), odds ratio [OR] = 1.40). HLA-DP allele analysis showed that DPA1*0201 and DPB1*0901, which were in strong linkage disequilibrium, were strongly associated with pediatric asthma (DPA1*0201: P = 5.5x10(-10), OR = 1.52, and DPB1*0901: P = 2.0x10(-7), OR = 1.49). Our findings show that genetic variants in the HLA-DP locus are associated with the risk of pediatric asthma in Asian populations.

引用

页数：9

共 42 条

[11] A Genome-Wide Association Study of Hypertension-Related Phenotypes in a Japanese Population
Hiura, Yumiko
Tabara, Yasuharu
Kokubo, Yoshihiro
Okamura, Tomonori
Miki, Tetsuo
Tomoike, Hitonobu
Iwai, Naoharu
[J]. CIRCULATION JOURNAL, 2010, 74 (11) : 2353 - 2359
[12] Howell WM, 1999, CLIN EXP ALLERGY, V29, P35
[13] Huang Hung-Wei, 2006, Acta Paediatr Taiwan, V47, P127
[14] S2554X mutation in the filaggrin gene is associated with allergen sensitization in the Japanese population
Imoto, Yoshimasa
Enomoto, Hisako
Fujieda, Shigeharu
Okamoto, Masayuki
Sakashita, Masafumi
Susuki, Dai
Okada, Masafumi
Hirota, Tomomitsu
Tamari, Mayumi
Ebe, Kouji
Arinami, Tadao
Noguchi, Emiko
[J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 125 (02) : 498 - 500
[15] Combined effect of tumour necrosis factor-α and interleukin-13 polymorphisms on bronchial hyperresponsiveness in Korean children with asthma
Kim, H-B.
Kang, M-J.
Lee, S-Y.
Jin, H-S.
Kim, J-H.
Kim, B-S.
Jang, S-O.
Lee, Y-C.
Sohn, M-H.
Kim, K-E.
Hong, S-J.
[J]. CLINICAL AND EXPERIMENTAL ALLERGY, 2008, 38 (05) : 774 - 780
[16] Comprehensive analysis of HLA genes in Takayasu arteritis in Japan
Kimura, A
Kitamura, H
Date, Y
Numano, F
[J]. INTERNATIONAL JOURNAL OF CARDIOLOGY, 1996, 54 : S61 - S69
[17] Kusunoki Takashi, 2009, Allergology International, V58, P543, DOI 10.2332/allergolint.09-OA-0085
[18] Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions
Li, Xingnan
Howard, Timothy D.
Zheng, Siqun L.
Haselkorn, Tmirah
Peters, Stephen P.
Meyers, Deborah A.
Bleecker, Eugene R.
[J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 125 (02) : 328 - 335
[19] Genotype Imputation
Li, Yun
Willer, Cristen
Sanna, Serena
Abecasis, Goncalo
[J]. ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, 2009, 10 : 387 - 406
[20] Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma
Moffatt, Miriam F.
Kabesch, Michael
Liang, Liming
Dixon, Anna L.
Strachan, David
Heath, Simon
Depner, Martin
von Berg, Andrea
Bufe, Albrecht
Rietschel, Ernst
Heinzmann, Andrea
Simma, Burkard
Frischer, Thomas
Willis-Owen, Saffron A. G.
Wong, Kenny C. C.
Illig, Thomas
Vogelberg, Christian
Weiland, Stephan K.
von Mutius, Erika
Abecasis, Goncalo R.
Farrall, Martin
Gut, Ivo G.
Lathrop, G. Mark
Cookson, William O. C.
[J]. NATURE, 2007, 448 (7152) : 470 - U5

← 1 2 3 4 5 →