Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness.
СтатьяПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
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Van Eerdewegh Paul, Little Randall D, Dupuis Josée, Del Mastro Richard G, Falls Kathy, Simon Jason, Torrey Dana, Pandit Sunil, McKenny Joyce, Braunschweiger Karen, Walsh Alison, Liu Ziying, Hayward Brooke, Folz Colleen, Manning Susan P, Bawa Alicia, Saracino Lisa, Thackston Michelle, Benchekroun Youssef, Capparell Neva, Wang Mei, Adair Ron, Feng Yun, Dubois JoAnn, FitzGerald Michael G, Huang Hui, Gibson René, Allen Kristina M, Pedan Alex, Danzig Melvyn R, Umland Shelby P, Egan Robert W, Cuss Francis M, Rorke Steuart, Clough Joanne B, Holloway John W, Holgate Stephen T, Keith Tim P
Аннотация
Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component. To date, linkage studies have identified more than a dozen genomic regions linked to asthma. In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P = 0.04 0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors. The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.