Elevated fractional exhaled nitric oxide and blood eosinophil counts are associated with a 17q21 asthma risk allele in adult subjects.
Elevated fractional exhaled nitric oxide and blood eosinophil counts are associated with a 17q21 asthma risk allele in adult subjects.
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DOI：
10.2147/jaa.s149183
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发表时间：
2018
影响因子：
3.2
通讯作者：
Mathur SK
中科院分区：
文献类型：
--
作者：
Schwantes EA;Evans MD;Cuskey A;Burford A;Smith JA;Lemanske RF Jr;Jarjour NN;Mathur SK
全基因组关联研究发现，17q21位点的单核苷酸多态性（snp）与儿童期发作哮喘的风险增加有关。对于这些snp如何影响成年哮喘患者，我们所知甚少。我们试图研究rs7216389 （17q21相关SNP）与哮喘特征（包括分数呼气一氧化氮（FeNO）、嗜酸性粒细胞计数和哮喘发病年龄）之间的关系。受试者按SNP rs7216389进行基因分型。收集2008 ~ 2015年FeNO测量值和外周血嗜酸性粒细胞计数的几何平均值。收集人口统计资料和病史，包括自我报告的过敏诊断和哮喘发病年龄。分离嗜酸性粒细胞、单核细胞和外周血单核细胞（PBMCs）检测ORMDL3的表达。分析157名基因型受试者（31CC、72CT和54TT）的FeNO水平和252名基因型受试者（46CC、122CT和84TT）的外周嗜酸性粒细胞计数。在哮喘受试者的亚组分析中，归因T等位基因的数量与哮喘发病年龄显著降低（P=0.03）和FeNO水平升高（几何平均TT 30.0 ppb, CT 20.0 ppb, CC 20.0 ppb， P=0.02）相关。在整个队列中，T等位基因与较高百分比的个体嗜酸性粒细胞计数相关（TT 45%, CT 26%, CC 24%， P=0.005）。嗜酸性粒细胞表达ORMDL3 mRNA和蛋白。在成人受试者中，SNP rs7216389的T等位基因数量与显著更高的FeNO水平和外周嗜酸性粒细胞计数相对应。ORMDL3在嗜酸性粒细胞中的表达表明它们可能参与介导与17q21位点相关的哮喘风险。
Genome-wide association studies identified single-nucleotide polymorphisms (SNPs) at the 17q21 locus conferring increased risk for childhood-onset asthma. Little is known about how these SNPs impact adult asthma patients. We sought to examine an adult population for associations between rs7216389 (17q21-associated SNP) and features of asthma including fractional exhaled nitric oxide (FeNO), eosinophil counts, and age of asthma onset. Subjects were genotyped at SNP rs7216389. The geometric mean of FeNO measurements and peripheral blood eosinophil counts from 2008 to 2015 were collected. Demographics and medical history were collected including self-reported allergy diagnoses and age of asthma onset. Eosinophils, monocytes, and peripheral blood mononuclear cells (PBMCs) were isolated for the examination of ORMDL3 expression. FeNO levels from 157 genotyped subjects (31CC, 72CT, and 54TT) and peripheral eosinophil counts from 252 genotyped subjects (46CC, 122CT, and 84TT) were analyzed. In a sub-group analysis of asthma subjects, the number of attributable T alleles was associated with significantly lower age of asthma onset (P=0.03) and greater FeNO levels (geometric mean 30.0 ppb TT, 20.0 ppb CT, 20.0 ppb CC, P=0.02). In the total cohort of subjects, the T allele was associated with a higher percentage of individual eosinophil counts >200/mm3 (45% TT, 26% CT, 24% CC, P=0.005). Eosinophils expressed ORMDL3 mRNA and protein. In adult subjects, the number of T alleles at SNP rs7216389 corresponds to significantly greater FeNO levels and peripheral eosinophil counts. The expression of ORMDL3 in eosinophils suggests that they may participate in mediating the asthma risk associated with the 17q21 locus.