Chromosome 11q13 and atopic asthma.
Asthma is a complex syndrome in which bronchial inflammation and smooth muscle hyperactivity lead to labile airflow obstruction. The commonest form of asthma is that due to atopy, which is an immune disorder where production of IgE to inhaled antigens leads to bronchial mucosal inflammation. The ultimate origins of asthma are interactive environmental and genetic factors. The genetics is acknowledged to be heterogeneous, and one chromosomal region of interest and controversy has been 11q13. To clarify the nature of the chromosome 11q13 effect in atopy and asthma, we conducted a genetic association study in subjects with marked atopic asthma and matched controls, which incorporated the study of 13 genetic variants over a distance of 10-12 cM and which took account of detailed immune and clinical phenotyping. Association with high IgE levels was limited to the interval flanked by D11S1335 and CD20 in a 0.8-Mb interval and was greatest for variants of Fc epsilonRIbeta and HTm4; these variants also associated with asthma (recurrent wheeze with labile airflow obstruction and need for regular inhaler treatment). At the more telomeric marker, D11S480, variants associated with asthma, but not with high IgE levels. The data might support the possibility of multiple loci relevant to atopic asthma on chromosome 11q13.
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Hematology/Oncology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Mao
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Kawada
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Gao
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Korzycka
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Donate
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Shaldon
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Coull
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Dubowitz
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Enomoto
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Ozawa
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Syed
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Horiuchi
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Khaeraja
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Khan
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Lin
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Flinter
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Beales
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Hagihara
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Inoko
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Shirakawa
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Hopkin
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D000483:Alleles; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005260:Female; D005787:Gene Frequency; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic