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

被引：107

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 [J].

Hiura, Yumiko ;

Tabara, Yasuharu ;

Kokubo, Yoshihiro ;

Okamura, Tomonori ;

Miki, Tetsuo ;

Tomoike, Hitonobu ;

Iwai, Naoharu .

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 [J].

Imoto, Yoshimasa ;

Enomoto, Hisako ;

Fujieda, Shigeharu ;

Okamoto, Masayuki ;

Sakashita, Masafumi ;

Susuki, Dai ;

Okada, Masafumi ;

Hirota, Tomomitsu ;

Tamari, Mayumi ;

Ebe, Kouji ;

Arinami, Tadao ;

Noguchi, Emiko .

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 [J].

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. .

CLINICAL AND EXPERIMENTAL ALLERGY, 2008, 38 (05) :774-780

[16] Comprehensive analysis of HLA genes in Takayasu arteritis in Japan [J].

Kimura, A ;

Kitamura, H ;

Date, Y ;

Numano, F .

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 [J].

Li, Xingnan ;

Howard, Timothy D. ;

Zheng, Siqun L. ;

Haselkorn, Tmirah ;

Peters, Stephen P. ;

Meyers, Deborah A. ;

Bleecker, Eugene R. .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 125 (02) :328-335

[19] Genotype Imputation [J].

Li, Yun ;

Willer, Cristen ;

Sanna, Serena ;

Abecasis, Goncalo .

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, 2009, 10 :387-406

[20] Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma [J].

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. .

NATURE, 2007, 448 (7152) :470-U5

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