Evidence for association and linkage between atopy, airway hyper-responsiveness, and the β subunit Glu237Gly variant of the high-affinity receptor for immunoglobulin E in the French-Canadian population
Evidence for association and linkage between atopy, airway hyper-responsiveness, and the β subunit Glu237Gly variant of the high-affinity receptor for immunoglobulin E in the French-Canadian population
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DOI：
10.1007/s002510000185
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发表时间：
2000-07-01
期刊：
影响因子：
3.2
通讯作者：
Raymond, V
中科院分区：
文献类型：
--
作者：
Laprise, C;Boulet, LP;Raymond, V
在检测到特应性与染色体11 q13标记之间的连锁后，在澳大利亚、英国和日本人群中报告了这种疾病与免疫球蛋白E高亲和力受体β亚基变体（Fc β RI-β，哮喘相关疾病的候选基因，共定位于同一区域）之间的关联。对其他几个族裔群体的调查未能复制这些观察结果。由于定义与哮喘相关的中间表型的复杂性，这种关联的检测可能会受到临床错误分类的阻碍。为了评估Fc β受体抑制剂β基因是否与法裔加拿大人群中的特应性和/或气道高反应性（AHR）有关，我们采用严格的哮喘和相关疾病标准，对200例受试者进行了病例对照研究。利用两种扩增难治性突变系统检测Ile 181 Leu和Glu 237 Gly Fc β-受体抑制剂-β序列变体。在特应性或AHR与Ile 181 Leu Fc β-受体抑制剂变异体之间未检测到相关性。然而，观察到特应性与Glu 237 Gly Fc β-谷氨酰胺受体抑制剂-β变体之间存在强相关性（比值比=12.25）。四个大的东部魁北克家庭（n=106名受试者）也被招募进行遗传连锁研究。我们观察到特应性与Glu 237 Gly Fc β-谷氨酰胺受体抑制剂-β变体（Z（max）=2.30）之间存在关联的暗示性证据。这项研究是第一个检测到过敏症和Glu 237 Gly Fc β-突变体之间存在关联的法裔加拿大人。我们的数据表明，特应性的易感位点位于染色体11 q13在这个群体。
Following detection of linkage between atopy and chromosome 11q13 markers, association between this disorder and variants of the beta subunit of the high-affinity receptor for immunoglobulin E (Fc epsilon RI-beta, a candidate gene for asthma-related conditions co-localizing within the same region) was reported in Australian, British and Japanese populations. Investigations in several other ethnic groups failed to replicate these observations. Due to the complexity of defining intermediate phenotypes related to asthma, detection of such associations may have been hampered by clinical misclassifications. To assess whether the Fc epsilon RI-beta gene was involved in atopy and/or airway hyperresponsiveness (AHR) in the French-Canadian population, we conducted a case-control study in 200 subjects using strict criteria for asthma and related conditions. The Ile181Leu and Glu237Gly Fc epsilon RI-beta sequence variants were tested exploiting two amplification refractory mutation systems. No association was detected between atopy or AHR and the Ile181Leu Fc epsilon RI-beta variant. However, a strong association was observed between atopy and the Glu237Gly Fc epsilon RI-beta variant (odds ratio=12.25). Four large Eastern Quebec families (n=106 subjects) were also recruited to perform a genetic linkage study. We observed suggestive evidence of linkage between atopy and the Glu237Gly Fc epsilon RI-beta Variant (Z(max)=2.30). This study is the first to detect the presence of an association between atopy and the Glu237Gly Fc epsilon RI-beta variant in French-Canadians. Our data suggest that a susceptibility locus for atopy is located on chromosome 11q13 in this population.