Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland
Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland
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DOI：
10.1164/ajrccm.164.11.2101086
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发表时间：
2001-12-01
影响因子：
24.7
通讯作者：
Stefansson, K
中科院分区：
文献类型：
--
作者：
Hakonarson, H;Bjornsdottir, US;Stefansson, K
大量的哮喘和特应性基因座已被报道，研究表明哮喘相关表型特应性、IgE水平升高和支气管高反应性与微卫星标记的等位基因和特定细胞因子/趋化因子和IgE调节基因的单核苷酸多态(SNPs)有关。尽管报告这些观察结果的研究令人信服，但它们中的大多数缺乏统计能力。我们评估了冰岛24个候选基因中SNPs的性质、模式和频率，并寻找与哮喘和特应性疾病的关联。我们发现了42个SNPs，平均小等位基因频率为20.3%(哮喘组)和20.7%(对照组)。20个SNP(48%)位于编码序列内，其中90%的SNP导致了蛋白质序列的预测变化。在对照组和特应性哮喘患者中，这些候选基因中的任何一个的SNPs等位基因频率没有发现差异。此外，包括269名特应性哮喘患者的连锁分析没有发现与这些基因相关的标记存在关联的证据。我们的结论是，这项研究没有提供证据支持这24个候选特应性和哮喘基因的变异显著影响特应性哮喘表型的表达或导致特应性哮喘易感性的观点。
Numerous asthma and atopy loci have been reported in studies demonstrating associations of the asthma-related phenotypes atopy, elevated IgE levels, and bronchial hyperresponsiveness with alleles of microsatellite markers and single-nucleotide polymorphisms (SNPs) within specific cytokine/chemokine and IgE-regulating genes. Although the studies reporting these observations are compelling, most of them lack statistical power. We assessed the nature, pattern, and frequency of SNPs in 24 candidate genes in Iceland and looked for associations with asthma and atopy. We Identified 42 SNPs with an average minor allele frequency of 20.3% (asthma) and 20.7% (control). Twenty SNPs (48%) were within coding sequences and 90% of those led to a predicted change in protein sequence. No differences were detected in the allelic frequencies of SNPs in any of these candidate genes between control subjects and the patients with atopic asthma. Moreover, linkage analysis that included 269 patients with atopic asthma uncovered no evidence of linkage to markers associated with these genes. We conclude that this study has failed to produce evidence in support of the notion that variations within these 24 candidate atopy and asthma genes significantly influence the expression of the atopic asthmatic phenotype or contribute to the susceptibility of atopic asthma.