Genetic Variation in Vascular Endothelial Growth Factor-A and Lung Function
Genetic Variation in Vascular Endothelial Growth Factor-A and Lung Function
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DOI：
10.1164/rccm.201112-2191oc
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发表时间：
2012-06-01
影响因子：
24.7
通讯作者：
Martinez, Fernando D.
中科院分区：
文献类型：
--
作者：
Simpson, Angela;Custovic, Adnan;Martinez, Fernando D.
基本原理：鉴于血管内皮生长因子（VEGF）在肺发育中的作用，我们假设VEGF-A的多态性可能与肺功能有关。目的：本研究旨在评估VEGF-A的遗传变异作为婴儿期至成年早期气道功能决定因素的作用。方法：在两个早产儿队列中纵向评估VEGF-A的五个单核苷酸多态性（SNPs）与肺功能之间的关联，并在婴儿中进行横断面评估。在患有哮喘的成人和儿童中进行了两个SNP的复制。我们研究了与肺功能最相关的SNP的功能（rs3025028）使用蛋白质印迹法测量纯合子中血浆VEGF-A（165 b）/panVEGF-A（165）的比率。在婴儿期的两个群体中，rs3025028的C等位基因纯合子具有显著较高的Vmax FRC、用力呼气流量、和用力呼气流量（25-75）与其他基因型组比较。在学龄前儿童（3岁）中，rs 3025028的C等位基因与显着较高的比气道电导相关，在学龄儿童的肺功能中也观察到类似的发现。对于FEV 1/FVC比值，在青少年和年轻成人（出生队列）中观察到类似的结果，然后在成人和学龄儿童哮喘患者中复制（横断面研究）。对于rs3025038，血浆VEGF-A（165 b）/panVEGF-A（165）在CC与GG纯合子中显著较高（P
Rationale: Given the role of vascular endothelial growth factor (VEGF) in lung development, we hypothesized that polymorphisms in VEGF-A may be associated with lung function.Objectives: The current study was designed to assess the role of genetic variants in VEGF-A as determinants of airway function from infancy through early adulthood.Methods: Association between five single-nucleotide polymorphisms (SNPs) in VEGF-A and lung function were assessed longitudinally in two unselected birth cohorts and cross-sectionally among infants. Replication with two SNPs was conducted in adults and children with asthma. We investigated the functionality of the SNP most consistently associated with lung function (rs3025028) using Western blotting to measure the ratio of plasma VEGF-A(165b)/panVEGF-A(165) among homozygotes.Measurements and Main Results: In two populations in infancy, C-allele homozygotes of rs3025028 had significantly higher VmaxFRC, forced expiratory flows, and forced expiratory flow(25-75) compared with other genotype groups. Among preschool children (age 3 yr), C allele of rs3025028 was associated with significantly higher specific airway conductance, with similar findings observed for lung function in school-age children. For FEV1/FVC ratio similar findings were observed among adolescents and young adults (birth cohort), and then replicated in adults and schoolchildren with asthma (cross-sectional studies). For rs3025038, plasma VEGF-A(165b)/panVEGF-A(165) was significantly higher among CC versus GG homozygotes (P