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Several genome scans have reported linkage of markers on chromosome 7p with asthma and related phenotypes in different populations. A fine mapping in Finnish and French-Canadian populations has associated the GPR154 gene (also known as G-protein-coupled receptor for asthma susceptibility, GPRA) with elevated IgE or asthma.To confirm chromosome 7p linkage and candidate gene association in Italian families with atopic asthma.In a two-phase approach, we first performed a linkage analysis of chromosome 7, and then a family-based association study on the GPR154 gene for allergic asthma phenotypes in the Italian population.The screening of 117 families with 19 microsatellite markers showed potential linkage for elevated IgE (P<0.002 at 22 cM from p-ter), asthma (P<0.005 at 44 cM), or atopy (P<0.005 at 54 cM). In the second phase of the present study, candidate gene GPR154, which is located in the phase one-linked region, was investigated in 211 families with seven single nucleotide polymorphisms (SNPs) that tag most haplotype variability, by the pedigree disequilibrium test. Elevated IgE levels were associated with two GPR154 gene SNPs (SNP 546333, P=0.0046; rs740 347, P=0.006), and with haplotypes in the global test (P=0.013). Haplotype analysis performed in nuclear families having at least 1 asthmatic parent showed a significant association with asthma (P=0.0173), atopy (P=0.0058), SPT (P=0.0025), and bronchial hyper reactivity (P=0.0163).These results support a susceptibility locus for asthma and related phenotypes on chromosome 7, and are in agreement with recent reports suggesting that a common susceptibility factor for atopic manifestations in asthma is likely conferred by the locus containing the GPR154 gene.

Original publication




Journal article


Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

Publication Date





83 - 89


Department of Mother and Child, Biology and Genetics, University of Verona, Verona, Italy.


Chromosomes, Human, Pair 7, Humans, Asthma, Genetic Predisposition to Disease, Immunoglobulin E, Receptors, G-Protein-Coupled, Genetic Markers, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Chi-Square Distribution, Microsatellite Repeats, Gene Frequency, Genotype, Haplotypes, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Software, European Continental Ancestry Group, Italy, Genetic Linkage