Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes
Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes
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DOI：
10.1016/j.jaci.2013.06.004
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发表时间：
2014-01-01
影响因子：
14.2
通讯作者：
Postma, Dirkje S.
中科院分区：
文献类型：
--
作者：
Kerkhof, Marjan;Boezen, H. Marike;Postma, Dirkje S.
背景资料：据推测，早期肺发育紊乱是慢性阻塞性肺疾病（COPD）易感性的基础。目的：我们研究了COPD的复制基因是否与6- 8岁儿童的短暂性早期喘息（TEW）和肺功能水平有关，以及子宫内和出生后的吸烟暴露是否与COPD的早期喘息（TEW）和肺功能水平有关。（环境烟草烟雾[ETS]）可以改变这些影响。方法：COPD相关基因15个基因20个单核苷酸多态性与TEW、FEV 1、用力肺活量（FVC）、在哮喘和螨过敏的预防和发病率（PIAMA）出生队列中研究FEV 1/FVC比值（n = 1996）并在儿童、父母和健康：生活方式和遗传构成（KOALA）和雅芳父母和儿童纵向研究（ALSPAC）队列中重复。AGER与FEV 1/FVC比值呈重复相关。ALSPAC中TNS 1与PAMA中TEW升高和FEV 1降低有关。TNS 1在PIAMA中与ETS相互作用，暴露儿童FEV 1降低。HHIP rs 1828591在PIAMA中与子宫内吸烟暴露相互作用，在ALSPAC中与ETS相互作用，未暴露儿童的肺功能较低。SERPINE 2、FAM 13 A和MMP 12与较高的FEV 1和FVC相关，SERPINE 2、HHIP和TGFB 1仅在PIATM中与子宫内香烟烟雾暴露相互作用，显示暴露对FEV 1的不利影响仅限于具有COPD风险最低基因型的儿童。我们的研究结果表明，至少有3个COPD基因与肺发育和肺生长有关，童年早期。此外，我们的研究结果表明，COPD基因参与了婴儿在子宫内和生命早期对烟雾暴露的肺反应。
Background: It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in childhood.Objective: We investigated whether replicated genes for COPD associate with transient early wheeze (TEW) and lung function levels in 6-to 8-year-old children and whether cigarette smoke exposure in utero and after birth (environmental tobacco smoke [ETS]) modifies these effects.Methods: The association of COPD-related genotypes of 20 single nucleotide polymorphisms in 15 genes with TEW, FEV1, forced vital capacity (FVC), and FEV1/FVC ratio was studied in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort (n = 1996) and replicated in the Child, parents and health: lifestyle and genetic constitution (KOALA) and Avon Longitudinal Study of Parents and Children (ALSPAC) cohorts.Results: AGER showed replicated association with FEV1/FVC ratio. TNS1 associated withmoreTEWinPIAMAand lower FEV1 in ALSPAC. TNS1 interacted with ETS in PIAMA, showing lower FEV1 in exposed children. HHIP rs1828591 interacted with cigarette smoke exposure in utero in PIAMA and with ETS in ALSPAC, with lower lung function in nonexposed children. SERPINE2, FAM13A, and MMP12 associated with higher FEV1 and FVC, and SERPINE2, HHIP, and TGFB1 interacted with cigarette smoke exposure in utero in PIAMAonly, showing adverse effects of exposure on FEV1 being limited to children with genotypes conferring the lowest risk of COPD.Conclusion: Our findings indicate relevant involvement of at least 3 COPD genes in lung development and lung growth by demonstrating associations pointing toward reduced airway caliber in early childhood. Furthermore, our results suggest that COPD genes are involved in the infant's lung response to smoke exposure in utero and in early life.