神经肽S受体1启动子DNA甲基化与哮喘及环境因素有关

2013/04/24

   摘要
   哮喘及过敏症都是受遗传和环境因素双重影响的复杂疾病,两者的关系或许可以通过表观遗传机制得以进一步厘清。神经肽S受体1(NPSR1)与哮喘及过敏症有关,有研究提示环境因素可以调节遗传危险度。我们的目的是研究NPSR1启动子区域DNA甲基化是否与哮喘及环境暴露有关。电泳迁移位移试验(EMSA)用以研究NPSR1启动子基因型及甲基化状态的潜在功能作用。EpiTYPER用于分析DNA甲基化。通过对成人严重哮喘的BIOAIR研究和瑞典出生队列BAMSE研究这两组队列特征明显的血液样品DNA甲基化分析,我们观察到启动子DNA甲基化和遗传变异影响细胞核蛋白与DNA结合,提示其功能上的相关性。值得注意的是,甲基化水平的差异与成人严重哮喘(P=0.00001)和儿童过敏性哮喘(P=0.01)有关,尽管差别微小但却有意义。此外,DNA甲基化与多种暴露有关,如两个GcP位点的甲基化与成人当前吸烟有关(p=0.005和0.04)、儿童的DAN甲基化与婴幼儿时期父母吸烟有关(p=0.02)以及取样的月份有关(p=0.01)等。概括地说,NPSR1启动子甲基化水平差异小,但与成人及儿童哮喘显著相关,而且与过敏症和特定的环境暴露等特征相关。遗传性变异和CpG位点甲基化状态似乎对NPSR1调节区域核蛋白的结合有影响,提示这一基因对哮喘和过敏症复杂的调节作用。

 

(王凌伟翻译 邱晨审校)
PLoS One. 2013;8(1):e53877. Epub 2013 Jan 23.


DNA Methylation in the Neuropeptide S Receptor 1 (NPSR1) Promoter in Relation to Asthma and Environmental Factors.
 

Reinius LE, Gref A, Sääf A, Acevedo N, Joerink M, Kupczyk M, D'Amato M, Bergström A, Melén E, Scheynius A,Dahlén SE; The BIOAIR Study Group, Pershagen G, Söderhäll C, Kere J.
 

Source
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden ; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.

Abstract
Asthma and allergy are complex disorders influenced by both inheritance and environment, a relationship that might be further clarified by epigenetics. Neuropeptide S Receptor 1 (NPSR1) has been associated with asthma and allergy and a study suggested modulation of the genetic risk by environmental factors. We aimed to study DNA methylation in the promoter region of NPSR1 in relation to asthma and environmental exposures. Electrophoretic Mobility Shift Assay (EMSA) was used to investigate potential functional roles of both genotypes and methylation status in the NPSR1 promoter. DNA methylation was analysed using EpiTYPER in blood samples from two well-characterized cohorts; the BIOAIR study of severe asthma in adults and the Swedish birth cohort BAMSE. We observed that DNA methylation and genetic variants in the promoter influenced the binding of nuclear proteins to DNA, suggesting functional relevance. Significant, although small, differences in methylation were related to both adult severe asthma (p = 0.0001) and childhood allergic asthma (p = 0.01). Furthermore, DNA methylation was associated with exposures such as current smoking in adults for two CpG sites (p = 0.005 and 0.04),  parental  smoking during infancy in the children (p = 0.02) and in which month the sample was taken (p = 0.01). In summary, DNA methylation levels in the promoter of NPSR1 showed small but significant associations with asthma, both in adults and in children, and to related traits such as allergy and certain environmental exposures. Both genetic variation and the methylated state of CpG sites seem to have an effect on the binding of nuclear proteins in the regulatory region of NPSR1 suggesting complex regulation of this gene in asthma and allergy.

 

PLoS One. 2013;8(1):e53877. Epub 2013 Jan 23.


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