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

Several genome,wide screens for asthma and related phenotypes have been pub lished to date but data on fine,mapping are scarce. For higher resolution w e performed a fine-mapping study with 2 cM average spacing in often discuss ed asthma candidate regions (2p, 5q, 6p, 7p, 9q, 11p, and 12q) to narrow do wn the regions of interest. All participants of a Caucasian family study (9 7 families with at least two affected sib pairs) were genotyped for 49 supp lementary 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), l ymphotoxin alpha (LTA), and neuronal nitric oxide synthase (NOS 1) genes. I n 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 test ed, 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 NOS I 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 map ping data enable us to cone fine asthma candidate regions, while variants o f EDN1 and NOS1, or nearby genes, may play an important role in this contex t. Hum Mutat 18:327-336, 2001. (C) 2001 Wiley-Liss, Inc.