Noguchi E, Ohtsuki Y, Tokunaga K, Yamaoka-Sageshima M, Ichikawa K, Aoki T, Shibasaki M, Arinami T
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Clin Exp Allergy. 2006 May;36(5):602-8. doi: 10.1111/j.1365-2222.2006.02471.x.
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.
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.
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.
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.
Our results confirm the involvement of ADAM33 in the development of childhood asthma among the Japanese.
哮喘是儿童期最常见的慢性疾病,哮喘急性发作是儿童发病和住院的重要原因。哮喘被认为是一种涉及遗传和环境因素的复杂疾病,通过全基因组筛查已确定了多个哮喘易感基因座。解整合素金属蛋白酶33(ADAM33)是2002年通过定位克隆发现的首个哮喘易感基因。
本研究旨在调查ADAM33中的单核苷酸多态性(SNP)是否与日本人群中的儿童哮喘相关。
利用通过特应性哮喘儿童确定的155个家庭(538名成员)的DNA,通过荧光相关光谱法对23个ADAM33 SNP进行基因分型。采用传递不平衡检验(TDT)进行基于家系的关联研究。
TDT显示,S+1、ST+4和T2 SNP的次要等位基因过度传递给哮喘患儿(P<0.05)。根据单倍型TDT,ADAM33的单倍型没有优先传递给哮喘患儿。
我们的结果证实了ADAM33参与了日本儿童哮喘的发病过程。