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Clin Epigenetics. 2017 Nov 7;9:121. doi: 10.1186/s13148-017-0421-8. eCollection 2017.

Epigenetic regulation of AXL and risk of childhood asthma symptoms.

Author information

1
Department of Preventive Medicine, USC Keck School of Medicine, 2001 N. Soto Street, Los Angeles, CA 90032 USA.
2
Department of Biological Sciences, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27695 USA.
3
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC 27710 USA.

Abstract

Background:

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.

Methods:

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.

Results:

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.

Conclusions:

AXL DNA methylation at birth was associated with higher risk for asthma-related symptoms in early childhood.

KEYWORDS:

Children; Epigenetics; Methylation

PMID:
29177020
PMCID:
PMC5688797
DOI:
10.1186/s13148-017-0421-8
[Indexed for MEDLINE]
Free PMC Article

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