Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations.
Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations.
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DOI：
10.1371/journal.pgen.1002170
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发表时间：
2011-07
期刊：
影响因子：
4.5
通讯作者：
Matsumoto K
中科院分区：
文献类型：
--
作者：
Noguchi E;Sakamoto H;Hirota T;Ochiai K;Imoto Y;Sakashita M;Kurosaka F;Akasawa A;Yoshihara S;Kanno N;Yamada Y;Shimojo N;Kohno Y;Suzuki Y;Kang MJ;Kwon JW;Hong SJ;Inoue K;Goto Y;Yamashita F;Asada T;Hirose H;Saito I;Fujieda S;Hizawa N;Sakamoto T;Masuko H;Nakamura Y;Nomura I;Tamari M;Arinami T;Yoshida T;Saito H;Matsumoto K
哮喘是一种受遗传和环境因素影响的复杂表型。我们对938名日本儿童哮喘患者和2，376名对照进行了全基因组关联研究（GWAS）。在一个独立的日本样本（818例和1，032名对照）和韩国样本（835例和421名对照）中，进一步对GWAS中显示强关联（P<1×10−8）的单核苷酸多态性（SNP）进行基因分型。SNP rs 987870位于HLA-DPA 1和HLA-DPB 1之间，在3个独立人群中与儿童哮喘一致相关（合并P = 2.3×10−10，比值比[OR]= 1.40）。 HLA-DP等位基因分析显示，DPA 1 *0201和DPB 1 *0901处于强连锁不平衡，与儿童哮喘密切相关（DPA 1 *0201：P = 5.5×10−10，OR = 1.52; DPB 1 *0901：P = 2.0×10−7，OR = 1.49）。 我们的研究结果表明，HLA-DP基因座的遗传变异与亚洲人群儿童哮喘的风险相关。哮喘是儿童最常见的慢性疾病，哮喘急性发作是儿童发病和住院的重要原因。在这里，利用人类遗传学的最新技术进步，我们进行了全基因组关联研究和后续验证研究，以确定哮喘的遗传变异。通过对6,428名亚洲人的研究，我们发现rs 987870和HLA-DPA 1 *0201/DPB 1 *0901与儿童哮喘相关。关联信号在HLA-DPB 2、胶原蛋白、XI型α 2（COL 11 A2）和维甲酸X受体β（RXRB）区域中被拉伸，但是在该区域中的强连锁不平衡使得难以特异性地鉴定致病变体。有趣的是，在本研究中与小儿哮喘（Th-2型免疫疾病）相关的SNP（或HLA-DP等位基因）赋予对Th-1型免疫疾病（如1型糖尿病和类风湿性关节炎）的保护。因此，本研究的相关结果可以部分解释哮喘与Th-1型免疫疾病之间的负相关关系，并可能有助于更好地理解Th-1/Th-2免疫疾病。
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<1×10−8) 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 = 2.3×10−10, 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 = 5.5×10−10, OR = 1.52, and DPB1*0901: P = 2.0×10−7, 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. Asthma is the most common chronic disorder in children, and asthma exacerbation is an important cause of childhood morbidity and hospitalization. Here, taking advantage of recent technological advances in human genetics, we performed a genome-wide association study and follow-up validation studies to identify genetic variants for asthma. By examining 6,428 Asians, we found rs987870 and HLA-DPA1*0201/DPB1*0901 were associated with pediatric asthma. The association signal was stretched in the region of HLA-DPB2, collagen, type XI, alpha 2 (COL11A2), and Retinoid X receptor beta (RXRB), but strong linkage disequilibrium in this region made it difficult to specifically identify causative variants. Interestingly, the SNP (or the HLA-DP allele) associated with pediatric asthma (Th-2 type immune diseases) in the present study confers protection against Th-1 type immune diseases, such as type 1 diabetes and rheumatoid arthritis. Therefore, the association results obtained in the present study could partially explain the inverse relationship between asthma and Th-1 type immune diseases and may lead to better understanding of Th-1/Th-2 immune diseases.
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影响因子：
158.5
作者：
Plenge, Robert M.;Seielstad, Mark;Gregersen, Peter K.
通讯作者：
Gregersen, Peter K.
影响因子：
5.5
作者：
Ovsyannikova, Inna G.;Jacobson, Robert M.;Poland, Gregory A.
通讯作者：
Poland, Gregory A.
DOI：
10.1165/rcmb.2006-0090oc
发表时间：
2007-04-01
影响因子：
6.4
作者：
Harada, Michishige;Nakashima, Kazuko;Tamari, Mayumi
通讯作者：
Tamari, Mayumi
DOI：
10.1093/bioinformatics/btq419
发表时间：
2010-09-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Pruim RJ;Welch RP;Sanna S;Teslovich TM;Chines PS;Gliedt TP;Boehnke M;Abecasis GR;Willer CJ
通讯作者：
Willer CJ
影响因子：
2.8
作者：
Choi, Jeong-Hee;Lee, Kyung-Wha;Park, Hae-Sim
通讯作者：
Park, Hae-Sim