A common FCER1B gene promoter polymorphism influences total serum IgE levels in a Japanese population
A common FCER1B gene promoter polymorphism influences total serum IgE levels in a Japanese population
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DOI：
10.1164/ajrccm.161.3.9903128
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发表时间：
2000-03-01
影响因子：
24.7
通讯作者：
Kawakami, Y
中科院分区：
文献类型：
--
作者：
Hizawa, N;Yamaguchi, E;Kawakami, Y
遗传因素在确定血清总IgE水平方面很重要。连锁分析已经在染色体11q13定位了一个或多个影响特应性表型的基因。FCER1B基因的变异已经被确定，它与发生特应性哮喘和支气管哮喘的风险增加有关。鉴于FCER1B基因的不确定功能后果和这些编码变异的低频率，我们筛选了24名特应性哮喘患者的新突变。在FCER1B的启动子区域发现了一个常见的-109C/T多态性，尽管在整个编码区没有发现变异。我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对226名健康对照者和226名哮喘患者的启动子多态性进行了基因分型。226名健康对照者-109T和-109C等位基因频率分别为0.697和0.303。哮喘组与健康对照组-109C/T多态性分布无显著差异。然而，Phe-109T等位基因的纯合性与226例哮喘患者血清总IgE水平升高相关（p = 0.0015）。当将哮喘发病年龄纳入分析时，获得了血清总IgE水平与-109C/T多态性之间关联的最有力证据（p = 0.0004）。我们的研究结果可能代表了遗传异质性以及参与总IgE水平调节的遗传和环境成分之间的复杂相互作用，提供了证据，证明FCER1B启动子区域的-109C/T多态性是迄今为止确定的影响日本人群血清总IgE水平的遗传因素之一。
Genetic factors are important in defining total serum IgE levels. Linkage analyses have localized a gene or genes that influence atopic phenotype at chromosome 11q13. Variants of the FCER1B gene have been identified, which are associated with an increased risk of developing atopy and bronchial asthma, Given uncertain functional consequences and low frequencies of these coding variants of FCER1B, we screened for new mutations using 24 subjects with atopic asthma. A common -109C/T polymorphism at the promoter region of FCER1B was Identified, although no variant was found In the entire coding region. We genotyped this promoter polymorphism in 226 healthy control subjects and 226 asthmatic subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Allele frequencies were 0.697 for -109T and 0.303 for -109C in 226 healthy control subjects. No significant difference in the distribution of -109C/T polymorphism was found between asthmatic subjects and healthy control subjects. A homozygosity for Phe-109T allele, however, was associated with increased total serum IgE levels in 226 subjects with asthma (p = 0.0015). The strongest evidence for an association between total serum IgE levels and -109C/T polymorphism (p = 0.0004) was obtained when age at onset of asthma was incorporated into the analysis. Our findings may represent genetic heterogeneity and complex interactions between genetic and environmental components involved in the regulation of total IgE levels, providing evidence that the -109C/T polymorphism of the FCER1B promoter region is one of the genetic factors identified thus far, which affects total serum IgE levels in a Japanese population.