Association of a disintegrin and metalloprotease 33 (ADAM33) gene with asthma in ethnically diverse populations.
BACKGROUND
Asthma is a complex genetic disease characterized by reversible intermittent airway obstruction and respiratory symptoms primarily caused by acute and chronic bronchial inflammation. Recently, a gene potentially involved in airway remodeling, a disintegrin and metalloprotease 33 (ADAM33), was implicated in asthma susceptibility.


OBJECTIVE
We sought to determine whether polymorphisms in ADAM33 are associated with asthma or closely related phenotypes in 4 different asthma populations.


METHODS
Eight single nucleotide polymorphisms (SNPs) were evaluated in the 3' portion of ADAM33 in 4 unique asthma populations (African American, US white, US Hispanic, and Dutch white). These SNPs were previously reported to be associated with asthma in white populations from the United States and United Kingdom.


RESULTS
Significant associations were observed with at least one SNP and asthma in each population (P =.0009-.04). Related phenotypes that included total serum IgE levels and skin test responsiveness were also associated (P =.003-.05). However, no single SNP was associated across all populations. Additionally, haplotype analysis revealed that no single haplotype accounted for asthma susceptibility risk, although potential risk haplotypes existed within some of the populations.


CONCLUSIONS
Replication of the original ADAM33 findings in these 4 additional asthma populations suggests that this gene (and perhaps others that interact with it) is important in the development and pathogenesis of asthma.
Howard
Timothy D
TD
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Postma
Dirkje S
DS
Jongepier
Hajo
H
Moore
Wendy C
WC
Koppelman
Gerard H
GH
Zheng
Siqun L
SL
Xu
Jianfeng
J
Bleecker
Eugene R
ER
Meyers
Deborah A
DA
D051722:ADAM Proteins; D001741:Black or African American; D001249:Asthma / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006630:Hispanic or Latino; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008666:Metalloendopeptidases / Q000235:genetics*; D009426:Netherlands / Q000208:ethnology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012882:Skin Tests; D044465:White People / Q000235:genetics*
D007073:Immunoglobulin E; D051722:ADAM Proteins; C450441:ADAM33 protein, human; D008666:Metalloendopeptidases