Prenatal and postnatal genetic influence on lung function development

被引：12

作者：

Kreiner-Moller, Eskil

Bisgaard, Hans

Bonnelykke, Klaus

机构：

[1] COPSAC the Copenhagen Prospective Studies on Asthma in Childhood, University of Copenhagen, Copenhagen University Hospital, Gentofte, Copenhagen

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2014年 / 134卷 / 05期

关键词：

Child; asthma; genetics; respiratory function tests; GENOME-WIDE ASSOCIATION; CHILDHOOD ASTHMA; METAANALYSIS; DISEASE; RISK; LOCI; VARIANTS; IMPUTATION; INFANCY;

D O I：

10.1016/j.jaci.2014.04.003

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: It is unknown to what extent adult lung function genes affect lung function development from birth to childhood. Objective: Our aim was to study the association of candidate genetic variants with neonatal lung function and lung function development until age 7 years. Methods: Lung function measurement by means of spirometry with the raised-volume thoracoabdominal compression technique and bronchial responsiveness to methacholine challenge were assessed in 411 high-risk newborns from the Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC(2000)) cohort. Measures were repeated at age 7 years. Genetic risk scores were calculated based on reported single nucleotide polymorphisms for adult lung function (FEV1/forced expiratory vital capacity [FVC] ratio and FEV1) as the number of risk alleles weighted on known effect size. These genetic risk scores were analyzed against lung function measures as z scores at birth (forced expiratory volume in 0.5 seconds [FEV0.5], forced expiratory flow at 50% of functional vital capacity [FEF50], and provocative dose of methacholine causing a 15% decrease in lung function [PD15]) and at age 7 years (FEV1, FEF50, and provocative dose of methacholine causing a 20% decrease in lung function [PD20]) and with development from birth to age 7 years (FEV0.5/1, FEF50, and PD15/20). Results: The genetic risk scores were not associated with lung function measures at age 1 month, but the FEV1/FVC genetic risk score was associated with reduced FEF50 values at age 7 years (P = .01) and similarly with reduced growth in FEF50 from birth to age 7 years (P = .02). This score was also associated with increased bronchial responsiveness (reduced PD20) at age 7 years (P = .02) and change in responsiveness from birth to age 7 years (P = .05). Conclusion: Lung function genetic variants identified in adults were not associated with neonatal lung function or bronchial responsiveness but with the development of these lung function measures during early childhood, suggesting a window of opportunity for interventions targeting these genetic mechanisms.

引用

页码：1036 / +

页数：22

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