ADAM33 polymorphisms are associated with aspirin-intolerant asthma in the Japanese population.
Multiple single nucleotide polymorphisms (SNPs) within ADAM33 have been reported to be associated with asthma and bronchial hyper-responsiveness in Caucasian populations. We examined whether these SNPs contribute to a predisposition to asthma, especially aspirin-intolerant asthma (AIA), in the Japanese population. Ten polymorphic sites (ST+4, ST+7, T1, T2, T+1, V-3, V-2, V-1, V4, V5) were genotyped in 102 AIA patients, 282 aspirin-tolerant asthma (ATA) patients and 120 control (CTR) subjects by direct sequencing. Haplotype frequencies were estimated by the expectation-maximization method. Differences in allele and haplotype frequencies among phenotypes were analyzed by the chi-square and permutation tests. ST+7, V-1 and V5 sites in the AIA group were significantly different from those in the ATA group (P=0.034-0.004) and from those in the CTR group (P=0.019-0.002). Haplotypes at three sites (ST+7, V-1, and V5) were significantly different in frequency between the AIA and ATA (P=0.008) or CTR (P=0.001) groups. Sequence variations in ADAM33 are likely to correlate with susceptibility to AIA in the Japanese population.
Sakagami
Takuro
T
Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan. takuro@bridge.ocn.ne.jp.|Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. takuro@bridge.ocn.ne.jp.
Jinnai
Nobuyoshi
N
Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Nakajima
Toshiaki
T
Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Sekigawa
Takashi
T
Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.|Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Hasegawa
Takashi
T
Niigata University Medical and Dental Hospital, Niigata, Japan.
Suzuki
Eiichi
E
Niigata University Medical and Dental Hospital, Niigata, Japan.
Inoue
Ituro
I
Division of Genetic Diagnosis, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Gejyo
Fumitake
F
Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.
D051722:ADAM Proteins / Q000235:genetics*; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D004361:Drug Tolerance / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051722:ADAM Proteins; C450441:ADAM33 protein, human; D001241:Aspirin