Gene Found Related to Asthma Susceptibility

A gene called ADAM33, which codes for the production of the protease sub-family known as metalloproteases, has been linked through genetic screening to susceptibility to asthma. The study was published in the July 10, 2002, online edition of Nature.

As part of an alliance with Schering-Plough (Kenilworth, NJ, USA) to develop therapies for asthma, researchers at Genome Therapeutics (Waltham, MA, USA) and the University of Southampton (UK) amassed clinical information and biological samples from over 450 families in the United States and the United Kingdom with members who suffer from asthma. Using the samples obtained, Genome Therapeutics employed its proprietary disease-specific gene identification platform to identify candidate genes linked to an increased likelihood of suffering from asthma.

Families with at least two children suffering from asthma were enrolled in the study. The affected subjects were required to have a diagnosis of asthma from a physician and be prescribed an asthma medication in order to be eligible. Following a genome-wide linkage analysis, the researchers identified several chromosomal regions as the likely location of the asthma genes, including chromosome 20p13. Further association studies on genes present in this chromosomal region confirmed that specific mutations in the ADAM33 gene were related to asthma susceptibility. The genetic analyses suggested that ADAM33 was involved in the generation of bronchial hyperresponsiveness (BHR).

"The airways in asthma patients undergo a number of changes such as thickening of the airway walls and subsequent narrowing of the airway passage,” stated Dr. Stephen Holgate, professor at the School of Medicine, University of Southampton, and a lead collaborator on the project. "These changes contribute to the overall airway responsiveness and related breathing problems in asthma. Our studies suggest ADAM33 plays a role in this remodeling and may underlie abnormalities in asthmatic airway function.”

The association of ADAM33 with BHR and possible links with airway remodeling offers new avenues of research into the underlying causes of asthma. Furthermore, discovery of susceptibility genes for asthma suggests that in the future it may become possible to identify those individuals who are predisposed to asthma and initiate therapy early to prevent or ameliorate the disease process before permanent changes occur.




Related Links:
Genome Therapeutics Corporation
Schering-Plough
University of Southampton