The discovery and role of ADAM33, a new candidate gene for asthma.
Asthma is a complex disorder in which major genetic and environmental factors interact to initiate the disease and propagate it as a chronic relapsing disorder. Until recently, genetic factors implicated in the disease pathogenesis have been restricted to variants in known molecules involved in the inflammatory or remodelling pathways. This review discusses evidence for a new susceptibility gene for asthma, ADAM33, which was identified by positional cloning and shown to be selectively expressed in mesenchymal but not immune or inflammatory cells. ADAM33 belongs to a family of membrane-anchored metalloproteinases that also have fusagenic, adhesion and intracellular signalling properties. ADAM33 might play a key role in predisposing to the reduced lung function characteristic of asthma, possibly by influencing airway wall remodelling.
Holloway
John W
JW
Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK. m.w.holloway@soton.ac.uk
Davies
Donna E
DE
Powell
Robert
R
Haitchi
Hans-Michael
HM
Keith
Tim P
TP
Holgate
Stephen T
ST
D051722:ADAM Proteins / Q000235:genetics* / Q000502:physiology*; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D003001:Cloning, Molecular; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008954:Models, Biological; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012143:Respiratory Physiological Phenomena
D051722:ADAM Proteins; C450441:ADAM33 protein, human