Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen.
BACKGROUND
A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy.


OBJECTIVE
The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan.


METHODS
We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods.


RESULTS
Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels.


CONCLUSIONS
These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.
Department of Health Promotion and Human Behaviour, Kyoto University Graduate School of Public Health, Kyoto, Japan.
L
L
Cheng
T
T
Enomoto
T
T
Hirota
M
M
Shimizu
N
N
Takahashi
M
M
Akahoshi
A
A
Matsuda
Y
Y
Dake
S
S
Doi
K
K
Enomoto
A
A
Yamasaki
S
S
Fukuda
X-Q
XQ
Mao
J M
JM
Hopkin
M
M
Tamari
T
T
Shirakawa
D051722:ADAM Proteins; D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D032485:Cryptomeria; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008666:Metalloendopeptidases / Q000235:genetics*; D011058:Pollen; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics*; D017422:Sequence Analysis, DNA
D051722:ADAM Proteins; C450441:ADAM33 protein, human; D008666:Metalloendopeptidases