G. Malerba et al., Chromosome 14 linkage analysis and mutation study of 2 serpin genes in allergic asthmatic families, J ALLERG CL, 107(4), 2001, pp. 654-658
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.