ADAM33 polymorphisms are associated with asthma susceptibility in a Japanese population.
BACKGROUND
Asthma is the most common chronic disorder in childhood, and asthma exacerbation is an important cause of childhood morbidity and hospitalization. Asthma is believed to be a complex disorder involving genetic and environmental factors, and several asthma susceptibility loci have been identified through genome-wide screening. A disintegrin and metalloprotease 33 (ADAM33) was the first asthma susceptibility gene to be discovered by positional cloning in 2002.


OBJECTIVE
The aim of the present study was to investigate whether single-nucleotide polymorphisms (SNPs) in ADAM33 are associated with childhood asthma in the Japanese population.


METHODS
Twenty-three ADAM33 SNPs were genotyped by fluorescence correlation spectroscopy with the use of DNA from 155 families (538 members) identified through children with atopic asthma. The transmission disequilibrium test (TDT) was performed for family-based association study.


RESULTS
TDT revealed that minor alleles of S+1, ST+4, and T2 SNPs were over-transmitted to asthma-affected offspring (P<0.05). According to the haplotype TDT, no haplotype of ADAM33 was transmitted preferentially to asthmatic offspring.


CONCLUSIONS
Our results confirm the involvement of ADAM33 in the development of childhood asthma among the Japanese.
Noguchi
E
E
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. enoguchi@md.tsukudba.ac.jp
Ohtsuki
Y
Y
Tokunaga
K
K
Yamaoka-Sageshima
M
M
Ichikawa
K
K
Aoki
T
T
Shibasaki
M
M
Arinami
T
T
D051722:ADAM Proteins / Q000235:genetics*; D000328:Adult; D001249:Asthma / Q000235:genetics*; D002648:Child; D019483:Disintegrins / Q000235:genetics; D005192:Family Health; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics; D010290:Parents; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D019483:Disintegrins; D007073:Immunoglobulin E; D051722:ADAM Proteins; C450441:ADAM33 protein, human