Linkage and association of childhood asthma with the chromosome 12 genes
Linkage and association of childhood asthma with the chromosome 12 genes
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DOI：
10.1007/s10038-003-0118-z
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发表时间：
2004-03-01
影响因子：
3.5
通讯作者：
Matsubara, Y
中科院分区：
文献类型：
--
作者：
Shao, CC;Suzuki, Y;Matsubara, Y
一些研究表明，在不同种族人群中，染色体12 q13 -24区域与支气管哮喘和相关表型相关。在日本人群中，一项全基因组研究未能显示该区域连锁的有力证据。在至少一份报告中显示与疾病相关的12号染色体基因包括：信号转导和转录激活因子6基因（STAT 6）、一氧化氮合成酶1基因（NOS 1）、干扰素γ基因（IFNG）和激活诱导的胞苷脱氨酶基因（AICDA）。为了评估日本人群中12号染色体与儿童哮喘之间的连锁，我们使用12号染色体上的18个微卫星标记对儿童哮喘家族进行了同胞对连锁分析。为探讨12号染色体候选基因与哮喘的相关性，比较了正常对照组和哮喘患者中STAT 6、NOS 1和IFNG的等位基因和重复多态性基因型分布。并对AICDA基因的单核苷酸多态性进行了研究。染色体12q24.23-q24.33区域显示与哮喘有连锁关系。NOS 1内含子2 GT重复序列和STAT 6外显子1 GT重复序列与哮喘相关。IFNG内含子1CA重复序列和AICDA的465 C/T均未显示与哮喘相关。我们的结果表明NOS 1和STAT 6是哮喘易感基因，染色体12 q24.23-q24.33区域还包含其他易感基因。
Several studies have shown linkage of chromosome region 12q13-24 to bronchial asthma and related phenotypes in ethnically diverse populations. In the Japanese population, a genome-wide study failed to show strong evidence of linkage of this region. Chromosome 12 genes that showed association with the disease in at least one report include: the signal transducer and activator of transcription 6 gene (STAT6), the nitrogen oxide synthetase 1 gene (NOS1), the interferon gamma gene (IFNG), and the activation-induced cytidine deaminase gene (AICDA). To evaluate the linkage between chromosome 12 and childhood asthma in the Japanese population, we performed sib-pair linkage analysis on childhood asthma families using 18 microsatellite markers on chromosome 12. To investigate association between chromosome 12 candidate genes and asthma, distributions of alleles and genotypes of repeat polymorphisms of STAT6, NOS1, and IFNG were compared between controls and patients. Single nucleotide polymorphism of AICDA was also investigated. Chromosome region 12q24.23-q24.33 showed suggestive linkage to asthma. The NOS1 intron 2 GT repeat and STAT6 exon 1 GT repeat were associated with asthma. Neither the IFNG intron 1 CA repeat nor 465C/T of AICDA showed any association with asthma. Our results suggest that NOS1 and STAT6 are asthma-susceptibility genes and that chromosome region 12q24.23-q24.33 contains other susceptibility gene(s).