哮喘联盟

   摘要
   背景：孕妇维生素D摄入不足是幼儿哮喘的一项危险因素，提示出生前的改变与维生素D应答基因有关，可能在出生后疾病的易感性中扮演重要角色。我们假设维生素D通路基因在胎儿中的发育活跃，且这些发育基因与哮喘易感性和控制性有关。
   方法：维生素D通路基因源自于PubMed和基因本体论的研究。主成分分析法被用于确定典型的肺发育基因。
   结果：维生素D调节基因在正常人和鼠发育的肺中高度表达（优势比OR 2.15，95% 置信区间 CI：1.69-2.74；OR 2.68，95% CI: 2.12-3.39）。38种维生素D通路基因在两种发育的肺中有＞63%的基因在发育晚期比发育早期表达的更好。永生化B细胞来源于95例哮喘受试者和其无哮喘的同胞，38种维生素D通路发育基因中有12种（31.6%）表达明显不同（OR 3.00，95% CI：1.43-6.21），而43种对照中有11 （29%）种基因相对于来自儿童哮喘管理项目中接受永生化-B细胞的受试者而言，表达有差异（OR 2.62， 95% CI：1.22-5.50）。4种基因包括LAMP3， PIP5K1B，SCARB2 和TXNIP在两组中已经被确定，每一种都在哮喘中显示出重要的生物合理性。
   结论：我们的结果证明，早期肺发育与哮喘相关的维生素D通路基因的表型有显著的相关性，并支持这一基因机制，以流行病学为基础的关于孕妇维生素D摄入与幼儿哮喘易感性关系的结果。
 

（苏楠 审校）
BMC Med Genomics. 2013 Nov 5;6(1):47. [Epub ahead of print]

 

Vitamin D related genes in lung development and asthma pathogenesis.
 

Kho AT, Sharma S, Qiu W, Gaedigk R, Klanderman B, Niu S, Anderson C, Leeder JS,
Weiss ST, Tantisira KG.
 

Abstract
BACKGROUND: Poor maternal vitamin D intake is a risk factor for subsequent childhood asthma, suggesting that in utero changes related to vitamin D responsive genes might play a crucial role in later disease susceptibility. We hypothesized that vitamin D pathway genes are developmentally active in the fetal lung and that these developmental genes would be associated with asthma susceptibility and regulation in asthma.
METHODS: Vitamin D pathway genes were derived from PubMed and Gene Ontology surveys. Principal component analysis was used to identify characteristic lung development genes.
RESULTS: Vitamin D regulated genes were markedly over-represented in normal human (odds ratio OR 2.15, 95% confidence interval CI: 1.69-2.74) and mouse (OR 2.68, 95% CI: 2.12-3.39) developing lung transcriptomes. 38 vitamin D pathway genes were in both developing lung transcriptomes with >63% of genes more highly expressed in the later than earlier stages of development. In immortalized B-cells derived from 95 asthmatics and their unaffected siblings, 12 of the 38 (31.6%) vitamin D pathway lung development genes were significantly differentially expressed (OR 3.00, 95% CI: 1.43-6.21), whereas 11 (29%) genes were significantly differentially expressed in 43 control versus vitamin D treated immortalized B-cells from Childhood Asthma Management Program subjects (OR 2.62, 95% CI: 1.22-5.50). 4 genes, LAMP3, PIP5K1B, SCARB2 and TXNIP were identified in both groups; each displays significant biologic plausibility for a role in asthma.
CONCLUSIONS: Our findings demonstrate a significant association between early lung development and asthma--related phenotypes for vitamin D pathway genes, supporting a genomic mechanistic basis for the epidemiologic observations relating maternal vitamin D intake and childhood asthma susceptibility.
 

BMC Med Genomics. 2013 Nov 5;6(1):47. [Epub ahead of print]