Pollution-Related Asthma Response in African American Children Traced to TET1 Gene

Published March 2016
Journal of Allergy and Clinical Immunology

Diesel exhaust particulates change the expression of the TET1 gene in airway epithelial cells, which may shed new light on why higher rates of asthma affect African American children.

This finding, published in March 2016 in the Journal of Allergy and Clinical Immunology, provides evidence that supports a long-suspected possible cause of asthma and the role played by traffic-related air pollution (TRAP).

“Our study demonstrated for the first time that DNA methylation at the TET1 promoter is associated with childhood asthma in African Americans, and methylation at the same CpG site was significantly associated with current exposure to TRAP,” says Hong Ji, PhD, lead author.

Under the direction of Gurjit (Neeru) Khurana Hershey, MD, PhD, Ji worked with colleagues in Asthma Research, Human Genetics and Biostatistics and Epidemiology.

The team studied nasal epithelial cells of African American children for DNA-derived methylation levels of the TET1 gene. They compared children with asthma against non-asthmatic siblings. They also overlaid the results with data about TRAP exposure.

The study identified TET1 and associated TET enzymes as possible direct players in the development of asthma. The team also observed that diesel exhaust particulates change the expression of the TET1 gene in airway epithelial cells. Specifically, asthma was significantly associated with both a loss of TET1 promoter methylation and increased levels of global 5-hydroxymethylcytosine (5-hmC).

The study adds to the large role TET1 already plays in human development. Other studies have linked the gene to memory, brain function, leukemia, and more, Ji says.

Armed with new understanding of asthma’s epigenetic underpinnings, Ji says researchers can begin using animal models to learn more about how TET1 and other epigenetic enzymes affect asthma development. Eventually, this line of research could lead to new therapies and treatments.