Association between ADAM33 polymorphisms and adult asthma in the Japanese population.
BACKGROUND
ADAM33, a member of the ADAM (a disintegrin and metalloprotease) family, is a putative asthma susceptibility gene recently identified by positional cloning. It is important to know whether the association exists in ethnically diverse populations.


OBJECTIVE
To assess whether genetic functional variants of ADAM33 relate to the susceptibility or some phenotypes in adult patients with bronchial asthma in a Japanese population.


METHODS
We searched for single nucleotide polymorphisms (SNPs) in ADAM33 by PCR-directed sequencing and identified 48 SNPs. Fourteen SNPs were selected with regard to the LD pattern, and genotyped by Taq-Man and PCR-RFLP methods. We conducted an association study of ADAM33 with 504 adult asthmatic patients and 651 controls, and haplotype analyses of related variants were performed.


RESULTS
Significant associations with asthma were found for the SNPs T1 (Met764Thr), T2 (Pro774Ser), S2 and V-3 (with the lowest P-value for T1, P = 0.0015; OR 0.63). We analysed the haplotype using these four polymorphisms, and found a positive association with haplotype CCTG (P = 0.0024).


CONCLUSIONS
Our results replicate associations reported recently in other ethnic populations, and suggest that the ADAM33 gene is involved in the development of asthma through genetic polymorphisms.
Hirota
T
T
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
Hasegawa
K
K
Obara
K
K
Matsuda
A
A
Akahoshi
M
M
Nakashima
K
K
Shirakawa
T
T
Doi
S
S
Fujita
K
K
Suzuki
Y
Y
Nakamura
Y
Y
Tamari
M
M
D051722:ADAM Proteins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D019483:Disintegrins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D019483:Disintegrins; D051722:ADAM Proteins; C450441:ADAM33 protein, human