Epigenetic regulation of AXL and risk of childhood asthma symptoms.
Epigenetic regulation of AXL and risk of childhood asthma symptoms.
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DOI：
10.1186/s13148-017-0421-8
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发表时间：
2017
影响因子：
5.7
通讯作者：
Breton CV
中科院分区：
文献类型：
--
作者：
Gao L;Millstein J;Siegmund KD;Dubeau L;Maguire R;Gilliland FD;Murphy SK;Hoyo C;Breton CV
AXL 是 TAM（TYRO3、AXL 和 MERTK）受体酪氨酸激酶之一，可能影响许多与免疫相关的健康状况。然而，AXL 在哮喘中的作用，包括其表观遗传调控，尚未得到广泛研究。我们调查了出生时 AXL DNA 甲基化与 6 岁时出现儿童哮喘症状的风险之间的关联。使用 Illumina HumanMmethylation450 阵列对儿童健康研究 (CHS) 中 246 名儿童的新生儿血斑中的 AXL 调节区多个 CpG 位点的 DNA 甲基化进行测量。拟合逻辑回归模型来评估哮喘症状和 DNA 甲基化之间的关联。使用焦磷酸测序技术对新生儿血斑样本进行评估，以评估研究结果在 1038 名中枢性低通气综合症 (CHS) 受试者的单独群体中的重复性。 AXL 基因型是从全基因组数据中提取的。出生时 AXL 基因中 CpG 的平均甲基化程度较高，与父母报告的喘息风险较高相关，并且这种关联在女孩中比男孩更强。这种关系反映了基因体区域 5' 端附近的甲基化状态，甲基化水平每升高 1%，与 6 岁时出现喘息的风险增加 72% 显着相关。使用焦磷酸测序复制了一个 CpG 位点 cg00360107 的关联。 AXL 甲基化增加也与癌症基因组图谱 (TCGA) 数据集中肺组织中该基因的 mRNA 表达水平较低相关。此外，AXL DNA 甲基化与潜在的遗传多态性密切相关。 出生时 AXL DNA 甲基化与儿童早期出现哮喘相关症状的较高风险相关。本文的在线版本 (10.1186/s13148-017-0421-8) 包含补充材料，可供授权用户使用。
AXL is one of the TAM (TYRO3, AXL and MERTK) receptor tyrosine kinases and may affect numerous immune-related health conditions. However, the role for AXL in asthma, including its epigenetic regulation, has not been extensively studied. We investigated the association between AXL 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 AXL 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. AXL genotypes were extracted from genome-wide data. Higher average methylation of CpGs in the AXL 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 AXL methylation was also associated with lower mRNA expression level of this gene in lung tissue from the Cancer Genome Atlas (TCGA) dataset. Furthermore, AXL DNA methylation was strongly linked to underlying genetic polymorphisms. AXL DNA methylation at birth was associated with higher risk for asthma-related symptoms in early childhood. The online version of this article (10.1186/s13148-017-0421-8) contains supplementary material, which is available to authorized users.
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影响因子：
4
作者：
Hess, J;Angel, P;Schorpp-Kistner, M
通讯作者：
Schorpp-Kistner, M
实现癌症基因组数据的共同愿景。
DOI：
10.1056/nejmp1607591
发表时间：
2016-09-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Grossman RL;Heath AP;Ferretti V;Varmus HE;Lowy DR;Kibbe WA;Staudt LM
通讯作者：
Staudt LM
影响因子：
13.6
作者：
Duijts, Liesbeth
通讯作者：
Duijts, Liesbeth
影响因子：
7.7
作者：
Gutierrez-Arcelus M;Lappalainen T;Montgomery SB;Buil A;Ongen H;Yurovsky A;Bryois J;Giger T;Romano L;Planchon A;Falconnet E;Bielser D;Gagnebin M;Padioleau I;Borel C;Letourneau A;Makrythanasis P;Guipponi M;Gehrig C;Antonarakis SE;Dermitzakis ET
通讯作者：
Dermitzakis ET
DOI：
10.1164/rccm.2111021
发表时间：
2002-07-01
影响因子：
24.7
作者：
Gauderman, WJ;Gilliland, GF;Peters, JM
通讯作者：
Peters, JM