Published Online: December 9, 2013
Over the past decades, multiple genes have been identified for the development of asthma, yet they only explain a limited proportion of asthma heritability. To find more of the hidden heritability of asthma the interaction between genetic and environmental factors needs to be assessed. Two well-known risk factors for childhood onset asthma likely interacting with the genetic background of the child are in utero and childhood tobacco smoke exposure.
In a Letter to the Editor in The Journal of Allergy & Clinical Immunology (JACI) Scholtens et al. performed a genome-wide interaction study on childhood asthma to identify genes that interact with in utero and childhood tobacco smoke exposure. They meta-analyzed data from nine studies participating in the GABRIEL consortium, including over 6,000 subjects, and replicated the findings in four independent studies of over 13,000 subjects. This genome wide approach has not previously been applied to discover interactions between genes and tobacco smoke exposure in asthma.
For in utero tobacco smoke exposure, the most prominent polymorphism was located on chromosome 18 near EPB41L3. This gene is involved in cell-cell junction and may play a in role in apoptosis. For childhood tobacco smoke exposure, the most prominent polymorphism was located on chromosome 6 near PACRG, which has an important role in motile cilia function and cilia morphogenesis. Ciliary dysfunction may impair mucus clearance from the airways and had been shown to affect asthma severity.
The authors identified new polymorphisms that showed suggestive evidence for interaction with in utero and childhood tobacco smoke exposure in the development of childhood onset asthma. These loci were yet unidentified by regular candidate gene or genome-wide association studies. Interactions between these SNPs and tobacco smoke exposure in utero and in childhood may explain part of the missing heritability of asthma.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.