Department of Preventive Medicine, USC Keck School of Medicine, 2001 N. Soto Street, Los Angeles, CA 90032 USA.
Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27695 USA.
Clin Epigenetics. 2017 Nov 7;9:121. doi: 10.1186/s13148-017-0421-8. eCollection 2017.
is one of the TAM (, and ) receptor tyrosine kinases and may affect numerous immune-related health conditions. However, the role for in asthma, including its epigenetic regulation, has not been extensively studied.
We investigated the association between DNA methylation at birth and risk of childhood asthma symptoms at age 6 years. DNA methylation of multiple CpG loci across the regulatory regions of was measured in newborn bloodspots using the Illumina HumanMethylation450 array on a subset of 246 children from the Children's Health Study (CHS). Logistic regression models were fitted to assess the association between asthma symptoms and DNA methylation. Findings were evaluated for replication in a separate population of 1038 CHS subjects using Pyrosequencing on newborn bloodspot samples. genotypes were extracted from genome-wide data.
Higher average methylation of CpGs in the gene at birth was associated with higher risk of parent-reported wheezing, and the association was stronger in girls than in boys. This relationship reflected the methylation status of the gene-body region near the 5' end, for which a 1% higher methylation level was significantly associated with a 72% increased risk of ever having wheezed by 6 years. The association of one CpG locus, cg00360107 was replicated using Pyrosequencing. Increased methylation was also associated with lower mRNA expression level of this gene in lung tissue from the Cancer Genome Atlas (TCGA) dataset. Furthermore, DNA methylation was strongly linked to underlying genetic polymorphisms.
DNA methylation at birth was associated with higher risk for asthma-related symptoms in early childhood.
是 TAM（TGF-β、TNF-α 和 IL-6）受体酪氨酸激酶家族的一员，可能影响多种与免疫相关的健康状况。然而， 对哮喘的作用，包括其表观遗传调控，尚未得到广泛研究。
我们研究了出生时 基因的 DNA 甲基化与 6 岁时儿童哮喘症状风险之间的关联。在儿童健康研究（CHS）的 246 名儿童的亚组中，使用 Illumina HumanMethylation450 阵列在新生儿血斑中测量了 多个调节区域的 CpG 位点的 基因 DNA 甲基化。使用逻辑回归模型评估哮喘症状与 DNA 甲基化之间的关联。使用 Pyrosequencing 在 1038 名 CHS 受试者的另一个人群中评估发现的复制情况，从全基因组数据中提取 基因型。
出生时 基因中 CpG 的平均甲基化水平较高与父母报告的喘息风险较高有关，且这种关联在女孩中比男孩中更强。这种关系反映了基因体区域靠近 5'端的甲基化状态，其中 1%的甲基化水平升高与 6 岁时曾经喘息的风险增加 72%显著相关。使用 Pyrosequencing 复制了一个 CpG 位点 cg00360107 的关联。来自癌症基因组图谱（TCGA）数据集的肺组织中， 基因的这种 CpG 位点的甲基化水平升高也与该基因的 mRNA 表达水平降低有关。此外， 基因的 DNA 甲基化与潜在的遗传多态性密切相关。
出生时的 DNA 甲基化与儿童早期哮喘相关症状的风险增加有关。
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