Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
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DOI：
10.1038/ng.323
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发表时间：
2009-03-01
期刊：
影响因子：
30.8
通讯作者：
Stefansson, Kari
中科院分区：
文献类型：
--
作者：
Gudbjartsson, Daniel F.;Bjornsdottir, Unnur S.;Stefansson, Kari
嗜酸性粒细胞是参与炎症反应的引发和传播的多效性白细胞，因此在炎症性疾病的发病机理中具有重要作用。在这里，我们描述了全基因组的关联扫描，以扫描影响9,392个冰岛血液中嗜酸性粒细胞计数的序列变体。在12,118名欧洲人和5,212个东亚人中，进一步研究了最重要的SNP。 SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10（-17），1.2 x 10（-10）和6.5 x 10（-19）。与哮喘相关的IL1RL1的SNP（p = 5.5 x 10（-12））在十个不同人群（7,996例病例和44,890个对照组）中。在WDR36，IL33和MYB上显示出暗示性与嗜酸性粒细胞计数相关的SNP也与特应性哮喘有关（P = 4.2 x 10（-6），2.2 x 10（-5）和2.4 x 10（-4）。我们还发现，在SH2B3中，第12季度的非同义SNP与六个不同人群（6,650例和40,621例对照）中的心肌梗塞显着相关（p = 8.6 x 10（-8））。
Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).