Association between ADAM33 polymorphisms and adult asthma in the Japanese population
Association between ADAM33 polymorphisms and adult asthma in the Japanese population
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DOI：
10.1111/j.1365-2222.2006.02522.x
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发表时间：
2006-07-01
影响因子：
6.1
通讯作者：
Tamari, M.
中科院分区：
文献类型：
--
作者：
Hirota, T.;Hasegawa, K.;Tamari, M.
ADAM33是一种崩解素和金属蛋白酶家族的成员，是最近通过定位克隆发现的一个假定的哮喘易感基因。重要的是要知道这种联系是否存在于不同种族的人群中。评估日本人群中成年支气管哮喘患者ADAM33基因功能变异是否与易感性或某些表型相关。通过pcr定向测序，我们在ADAM33中寻找了48个单核苷酸多态性（snp）。从LD模式中选择14个snp，采用Taq-Man和PCR-RFLP方法分型。我们进行了ADAM33与504名成年哮喘患者和651名对照者的关联研究，并对相关变异进行了单倍型分析。snp T1 （Met764Thr）、T2 （Pro774Ser）、S2和V-3与哮喘有显著相关性（T1的P值最低，P=0.0015; OR 0.63）。我们利用这四个多态性对单倍型进行分析，发现CCTG与单倍型呈正相关（P=0.0024）。我们的研究结果重复了最近在其他种族人群中报道的关联，并表明ADAM33基因通过遗传多态性参与哮喘的发展。
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.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.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.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).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.