Simon Thomas N, Wilkinson J, Lonjou C, Morton N E, Holgate S T
Human Genetics, and Respiratory Cell and Molecular Biology Division, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1268-72. doi: 10.1164/ajrccm.162.4.9909078.
Previous studies have suggested that atopy is linked to the beta chain of the high affinity IgE receptor (Fcepsilon R1-beta) on chromosome 11q13. Fcepsilon R1-beta polymorphisms, I181L, V183L, and E237G, are reported to be associated with asthma and atopy. The aim of this study was to investigate linkage to Fcepsilon R1-beta in a UK population and to assess the frequency of the polymorphisms and their association with asthma and atopy. A sample of 131 families was recruited at random with a sample of 109 families ascertained via an asthmatic proband. Each subject completed a written and video-assisted questionnaire and underwent bronchial challenge and skin prick testing. Serum total and specific IgE levels were measured. Quantitative scores were derived for asthma and atopy using principal component analysis. Four microsatellite markers were genotyped, including Fcepsilon R1-beta. The frequency of the I181L and V183L polymorphisms were determined by sequencing, and the E237G polymorphism was determined using the amplification refractory mutation system. We found no evidence for linkage to Fcepsilon R1-beta and only weak evidence for linkage to the less informative marker E237G. We found no examples of the I181L/V183L polymorphism in our population sample. Our study has failed to strengthen the evidence for a candidate gene on chromosome 11q13.
以往研究表明,特应性与位于11q13染色体上的高亲和力IgE受体(Fcepsilon R1-β)的β链有关。据报道,Fcepsilon R1-β基因多态性I181L、V183L和E237G与哮喘和特应性相关。本研究的目的是在英国人群中研究与Fcepsilon R1-β的连锁关系,并评估这些多态性的频率及其与哮喘和特应性的关联。随机招募了131个家庭的样本,另有109个家庭通过哮喘先证者确定。每位受试者完成了一份书面和视频辅助问卷,并接受了支气管激发试验和皮肤点刺试验。测量了血清总IgE和特异性IgE水平。使用主成分分析得出哮喘和特应性的定量评分。对包括Fcepsilon R1-β在内的四个微卫星标记进行基因分型。通过测序确定I181L和V183L多态性的频率,使用扩增阻滞突变系统确定E237G多态性。我们没有发现与Fcepsilon R1-β连锁的证据,仅发现与信息较少的标记E237G有微弱的连锁证据。在我们的人群样本中未发现I181L/V183L多态性的实例。我们的研究未能加强11q13染色体上候选基因的证据。