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

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