背景:胆红素具有抗氧化特性,正常范围内的水平升高与成人肺功能改善和哮喘风险降低有关,但是对幼儿的研究很少。这里,我们在两个独立出生队列中调查了早年胆红素与学龄前呼吸健康终点之间的关联.
方法:在COPSAC2010(哥本哈根2010年儿童期哮喘前瞻性研究)和VDAART(维生素D减少哮喘前试验)队列中评估了年龄为0.5、1.5和6岁的胆红素代谢物。对胆红素代谢产物水平与哮喘的关系进行Meta分析,感染,肺功能,和过敏致敏直到6岁。探索了与葡萄糖醛酸基转移酶家族1成员A1(UGT1A)基因型编码胆红素代谢酶的相互作用,和代谢组学数据被整合以研究潜在的机制。
结果:胆红素增加(Z,Z)在1.5-3岁时与变应性致敏的风险增加相关(调整后的相对风险[aRR]=1.85[1.20-2.85],p=0.005),和6岁的胆红素(Z,Z)还显示出与6岁时过敏致敏相关的趋势(aRR=1.31[0.97-1.77],p=0.08),这表明6岁胆红素(Z,Z)xUGT1A基因型。Further,胆红素增加(E,E),胆红素(Z,Z),1.5-3岁时胆绿素与6岁时用力呼气量较低相关(aRR范围=0.81-0.91,p<0.049),但与UGT1A基因型无显著交互作用(p交互作用>0.05)。网络分析显示胆红素代谢与酰基肉碱之间存在显着相关性。胆红素代谢物与哮喘和感染的风险之间没有关联。
结论:生命早期的胆红素代谢可能在儿童呼吸健康中起作用,特别是在具有特定UGT1A基因型的儿童中。
背景:伦贝克基金会(批准号R16-A1694),卫生部(赠款编号903516),丹麦战略研究委员会(批准号0603-00280B),和首都地区研究基金会为COPSAC研究中心提供了核心支持。该项目已根据欧盟的“地平线2020”研究和创新计划(赠款协议编号:946228)。维生素D产前哮喘减少试验(VDDART,ClinicalTrials.gov标识符:NCT00920621)受来自NHLBI的授权U01HL091528支持,U54TR001012来自国家推进转化科学中心(NCATS)。VDAART的代谢组学工作得到了国家心脏的支持,肺,和血液研究所(NHLBI)授予R01HL123915和R01HL141826。S.T.W.由NHLBI的R01HL091528支持,导演办公室的UG3OD023268,国立卫生研究院,和来自NHLBI的P01HL132825。
BACKGROUND: Bilirubin has antioxidant properties, and elevated levels within the normal range have been associated with improved lung function and decreased risk of asthma in adults, but studies of young children are scarce. Here, we investigate associations between bilirubin in early life and respiratory health endpoints during preschool age in two independent birth cohorts.
METHODS: Bilirubin metabolites were assessed at ages 0.5, 1.5, and 6 years in COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) and ages 1, 3, and 6 years in the VDAART (The Vitamin D Antenatal Asthma Reduction Trial) cohort. Meta-analyses were done to summarize the relationship between levels of bilirubin metabolites and asthma, infections, lung function, and allergic sensitization until age 6 across the cohorts. Interaction with the glucuronosyltransferase family 1 member A1 (UGT1A) genotype encoding for an enzyme in the bilirubin metabolism was explored, and metabolomics data were integrated to study underlying mechanisms.
RESULTS: Increasing bilirubin (Z,Z) at ages 1.5-3 years was associated with an increased risk of allergic sensitization (adjusted relative risk [aRR] = 1.85 [1.20-2.85], p = 0.005), and age 6 bilirubin (Z,Z) also showed a trend of association with allergic sensitization at age 6 (aRR = 1.31 [0.97-1.77], p = 0.08), which showed significant interaction for the age 6 bilirubin (Z,Z)xUGT1A genotype. Further, increasing bilirubin (E,E), bilirubin (Z,Z), and biliverdin at ages 1.5-3 years was associated with a lower forced expiratory volume at age 6 (aRR range = 0.81-0.91, p < 0.049) but without a significant interaction with the UGT1A genotype (p interactions > 0.05). Network analysis showed a significant correlation between bilirubin metabolism and acyl carnitines. There were no associations between bilirubin metabolites and the risk of asthma and infections.
CONCLUSIONS: Bilirubin metabolism in early life may play a role in childhood respiratory health, particularly in children with specific UGT1A genotypes.
BACKGROUND: The Lundbeck Foundation (Grant no R16-A1694), The Ministry of Health (Grant no 903516), Danish Council for Strategic Research (Grant no 0603-00280B), and The Capital Region Research Foundation have provided core support to the COPSAC research center. This project has received funding from the European Research Council (ERC) under the European Union\'s Horizon 2020 research and innovation programme (grant agreement No. 946228). The Vitamin D Antenatal Asthma Reduction Trial (VDDART, ClinicalTrials.gov identifier: NCT00920621) was supported by grant U01HL091528 from NHLBI, U54TR001012 from the National Centers for Advancing Translational Sciences (NCATS). Metabolomics work by VDAART was supported by the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL123915 and R01HL141826. S.T.W. was supported by R01HL091528 from the NHLBI, UG3OD023268 from Office of The Director, National Institute of Health, and P01HL132825 from the NHLBI.