Chromosome 14 linkage analysis and mutation study of 2 serpin genes in allergic asthmatic families

Background: Genome and chromosome screens reported DNA markers on chromosom e 14 linked to allergic asthma or intermediate phenotypes in several popula tions. Objective: We sought to perform a linkage study on chromosome 14 and a furt her association study on candidate genes mapped in the region found to be l inked to allergic asthma or intermediate phenotypes. Methods: The study consisted of a sample of 189 families (847 genotyped ind ividuals) from a restricted geographic area in northeastern Italy. The subj ects were characterized for the following phenotypes: allergic asthma, tota l serum IgE levels. skin prick test responses, and bronchial hyperresponsiv eness (BHR) to methacholine. Genotyping was done with 14 DNA markers and 4 polymorphisms in the genes encoding alpha (1)-antitrypsin and alpha (1)-ant ichymotrypsin (ACT). Results: Multipoint analysis indicated a potential linkage of BHR with mark er D14S617 (nonparametric linkage z score = 2.32, P = .01). Transmission di sequilibrium of Thr -15Ala in the gene encoding ACT was observed with all t he phenotypes investigated: allergic asthma, BHR. total IgE levels, or skin prick test responses (P = .041,.02,.0053, or .026, respectively). Conclusion: Chromosome 14 screening and transmission disequilibrium testing on the gene encoding ACT suggest that it or a closely located gene may be involved in susceptibility to allergic asthma in the Italian population.