Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes.

Immervoll, T; Loesgen, S; Dütsch, G; Gohlke, H; Herbon, N; Klugbauer, S; Dempfle, A; Bickeböller, H; Becker-Follmann, J; Rüschendorf, F; Saar, K; Reis, A; Wichmann, H E; Wjst, M

Immervoll, T; Loesgen, S; Dütsch, G; Gohlke, H; Herbon, N; Klugbauer, S; Dempfle, A; Bickeböller, H; Becker-Follmann, J; Rüschendorf, F; Saar, K; Reis, A; Wichmann, H E; Wjst, M.

Afiliación

Immervoll T; GSF-National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany. immervoll@gsf.de

Hum Mutat ; 18(4): 327-36, 2001 Oct.

Article en En | MEDLINE | ID: mdl-11668616

RESUMEN

Several genome-wide screens for asthma and related phenotypes have been published to date but data on fine-mapping are scarce. For higher resolution we performed a fine-mapping study with 2 cM average spacing in often discussed asthma candidate regions (2p, 5q, 6p, 7p, 9q, 11p, and 12q) to narrow down the regions of interest. All participants of a Caucasian family study (97 families with at least two affected sib pairs) were genotyped for 49 supplementary polymorphic dinucleotide markers. Our results indicate increased evidence for linkage on chromosome 6p, 9q, and 12q. These candidate regions were further analyzed with SNP polymorphisms in the endothelin 1 (EDN1), lymphotoxin alpha (LTA), and neuronal nitric oxide synthase (NOS1) genes. In addition, IL4 -590C>T and IL10 -592C>A, localized on chromosomes 5q and 1q, respectively, have been analyzed for SNP association. Of the six SNPs tested, four revealed weak association with the examined phenotypes. These are the IL10 -592C>A SNP in the interleukin 10 gene (p=0.036 for eosinophil cell counts), the 4124T>C SNP in EDN1 (p=0.044 for asthma), the 3391C>T SNP in NOS1 with eosinophil cell counts (p=0.0086), and the 5266C>T polymorphism, also in the NOS1 gene, for high IgE levels (p=0.022). In summary, fine mapping data enable us to confine asthma candidate regions, while variants of EDN1 and NOS1, or nearby genes, may play an important role in this context.

Asunto(s)

Asma/genética; Mapeo Cromosómico; Ligamiento Genético/genética; Predisposición Genética a la Enfermedad/genética; Polimorfismo de Nucleótido Simple/genética; Cromosomas Humanos/genética; Endotelina-1/genética; Eosinófilos; Exones; Genotipo; Humanos; Interleucina-10/genética; Interleucina-4/genética; Intrones; Recuento de Leucocitos; Linfotoxina-alfa/genética; Repeticiones de Microsatélite/genética; Óxido Nítrico Sintasa/genética; Óxido Nítrico Sintasa de Tipo I; Fenotipo; Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción; Población Blanca/genética

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Mapeo Cromosómico / Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple / Ligamiento Genético Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Hum Mutat Asunto de la revista: GENETICA MEDICA Año: 2001 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

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