KIF3A Gene Variation Provides Key Clues for Asthma-Eczema Connection

Published August 1, 2017 | Journal of Allergy and Clinical Immunology 

Scientists and clinicians observed long ago that eczema often precedes the development of asthma in children. The bigger scientific question has involved uncovering the common link that connects the skin and the lungs, leading to the progression of allergy between the two.

In a genetic variation of the protein-encoding gene KIF3A, a susceptibility locus for both conditions, researchers might have found the answer. First though, they had to weigh the effects of both eczema and allergic rhinitis (AR), an inflammation of the nasal mucous membrane that also has an asthma association.

The team analyzed the association between KIF3A’s single nucleotide polymorphisms, both alone and in combination with eczema and AR, and discovered an asthma/eczema link that was independent of AR. The wide-ranging study involved the Divisions of Asthma Research, Human Genetics, Biomedical Informatics, Biostatistics and Epidemiology, the Center for Autoimmune Genomics and Etiology, and several departments from the University of Cincinnati.

It was led by senior author Gurjit Khurana Hershey, MD, PhD, and Lisa Johansson, PhD, both of Asthma Research. Hershey is the division’s Director. Human Genetics’ Lisa Martin, PhD, also played a key role.

Data was mined from the Greater Cincinnati Pediatric Clinic Repository, a biorepository of samples from more than 7,000 children. The team was struck by the strong specificity of the association between KIF3A and the eczema plus asthma phenotype.

“In contrast,” Hershey and Johansson say, “allergic rhinitis, which is also an allergic disorder, was not a significant factor. Furthermore, KIF3A was not associated with eczema alone without comorbid asthma, suggesting that it truly identifies children with eczema who progress to develop asthma.”

Now, researchers are working to determine how KIF3A causes a dysfunctional epithelial barrier that leads to and then asthma in a cascade effect.

An image showing the associations between tagging single nucleotide polymorphisms in the KIF3A gene and allergic phenotypes compared to non-allergic controls.

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An image showing the percentage of all asthmatic children who also had co-morbid eczema or allergic rhinitis.

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A photo of Lisa Johansson, PhD.

Lisa Johansson, PhD

A photo of Gurjit Khurana Hershey.

Gurjit Khurana Hershey, MD, PhD

Citation

Johansson E, Biagini Myers JM, Martin LJ, He H, Pilipenko V, Mersha T, Weirauch M, Salomonis N, Ryan P, LeMasters GK, Bernstein DI, Lockey J, Khurana Hershey GK. KIF3A genetic variation is associated with pediatric asthma in the presence of eczema independent of allergic rhinitis. J Allergy Clin Immunol. 2017 Aug;140(2):595-598 e595.