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Connecting an asthma gene to leukemia

Aug. 2, 2018, 10:00 AM

A receptor previously implicated in asthma may also play roles in other allergic diseases and in leukemia, Vanderbilt researchers have discovered.

The investigators, led by Melissa Bloodworth, PhD, and Mark Rusznak, performed a phenome-wide association study (PheWAS) to search for associations between known variants in the ST2 gene and diagnoses in medical records. The ST2 gene encodes a receptor for IL-33, a central mediator of allergic inflammation in the lung. Genome-wide association studies (GWASs) have previously identified ST2 genetic variants associated with asthma.

The researchers found that specific ST2 variants associated with other allergic conditions, and they confirmed associations with asthma. They also uncovered a novel association of two ST2 variants with forms of leukemia.

The findings, reported in the Journal of Allergy and Clinical Immunology, establish the first genetic link between ST2 and leukemia, supporting further investigation of the IL-33/ST2 signaling pathway in leukemia. They also demonstrate the value of PheWAS in identifying novel disease connections for existing gene variants.

PheWAS was developed by Joshua Denny, MD, and colleagues in the Center for Precision Medicine. Other members of the Vanderbilt team included Lisa Bastarache, MS, Janey Wang, MS, and R. Stokes Peebles, MD.

This research was supported by grants from the National Institutes of Health (AI124456, AI095227, AI111820, GM007347, AI118376, TR000445, LM010685) and the Veterans Health Administration (BX000624).

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