class="Heading">Background id="Par1" class="Para">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. class="Heading">Methods id="Par2" class="Para">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 Childrena€?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. class="Heading">Results id="Par3" class="Para">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 5a€2 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. class="Heading">Conclusions id="Par4" class="Para">AXL DNA methylation at birth was associated with higher risk for asthma-related symptoms in early childhood.
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机译：class =“ Heading”>背景 id =“ Par1” class =“ Para”> AXL 是TAM之一（ TYRO3 ， AXL 和 MERTK ）受体酪氨酸激酶，可能会影响许多与免疫相关的健康状况。但是， 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。 class =“ Heading”>方法 <我们研究了出生时 AXL DNA甲基化与6岁儿童哮喘病风险之间的关系。使用Illumina HumanMethylation450阵列，对来自儿童健康研究（CHS）的246名儿童的子集，在新生血斑中测量了跨 AXL 调控区域的多个CpG基因位点的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。使用焦磷酸测序对新生儿血斑样本在1038名CHS受试者的单独人群中评估发现的复制。从整个基因组数据中提取了 AXL 基因型。 class =“ Heading”>结果 id =“ Par3” class =“ Para出生时 AXL 基因中CpG的平均甲基化较高与父母报告的喘息风险较高有关，女孩的这种关联比男孩的关联强。这种关系反映了5a€2末端附近的基因体区域的甲基化状态，为此，甲基化水平高1％时，患风化6 -6年的风险增加72％。使用焦磷酸测序法复制了一个CpG基因座cg00360107的关联。 AXL 甲基化的增加也与癌症基因组图谱（TCGA）数据集在肺组织中该基因的mRNA表达水平降低有关。此外， AXL DNA甲基化与潜在的遗传多态性密切相关。 class =“ Heading”>结论 id =“ Par4”类=“ Para”> AXL 出生时的DNA甲基化与儿童早期哮喘相关症状的高风险相关。
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