Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness.
Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.
Van Eerdewegh
Paul
P
Genome Therapeutics Corporation, 100 Beaver St, Waltham, Massachusetts 02453, USA.
Little
Randall D
RD
Dupuis
Josée
J
Del Mastro
Richard G
RG
Falls
Kathy
K
Simon
Jason
J
Torrey
Dana
D
Pandit
Sunil
S
McKenny
Joyce
J
Braunschweiger
Karen
K
Walsh
Alison
A
Liu
Ziying
Z
Hayward
Brooke
B
Folz
Colleen
C
Manning
Susan P
SP
Bawa
Alicia
A
Saracino
Lisa
L
Thackston
Michelle
M
Benchekroun
Youssef
Y
Capparell
Neva
N
Wang
Mei
M
Adair
Ron
R
Feng
Yun
Y
Dubois
JoAnn
J
FitzGerald
Michael G
MG
Huang
Hui
H
Gibson
René
R
Allen
Kristina M
KM
Pedan
Alex
A
Danzig
Melvyn R
MR
Umland
Shelby P
SP
Egan
Robert W
RW
Cuss
Francis M
FM
Rorke
Steuart
S
Clough
Joanne B
JB
Holloway
John W
JW
Holgate
Stephen T
ST
Keith
Tim P
TP
D051722:ADAM Proteins; D001249:Asthma / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D005091:Exons; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium / Q000235:genetics; D008126:Lod Score; D008666:Metalloendopeptidases / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D006113:United Kingdom; D014481:United States; D044465:White People / Q000235:genetics
D051722:ADAM Proteins; C450441:ADAM33 protein, human; D008666:Metalloendopeptidases