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Am. J. Respir. Crit. Care Med., Volume 162, Number 4, October 2000, 1268-1272

Linkage Analysis of Markers on Chromosome 11q13 with Asthma and Atopy in a United Kingdom Population

N. SIMON THOMAS, JANE WILKINSON, CHRISTINE LONJOU, NEWTON E. MORTON, and STEPHEN T. HOLGATE

Human Genetics, and Respiratory Cell and Molecular Biology Division, University of Southampton, Southampton General Hospital, Southampton, United Kingdom

Previous studies have suggested that atopy is linked to the beta chain of the high affinity IgE receptor (Fcvarepsilon R1-beta ) on chromosome 11q13. Fcvarepsilon 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 Fcvarepsilon 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 Fcvarepsilon 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 Fcvarepsilon 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.




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