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

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• 作者：Giovanni Malerba ; Cristina Patuzzo ; Elisabetta Trabetti ; Maria C. Lauciello ; Roberta Galavotti ; Lydia Pescollderungg ; Michael B. Whalen ; Giovanna Zanoni ; Laura C. Martinati ; Attilio L. Boner ; Pier Franco Pignatti
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2001
• 出版时间：April 2001
• 年：2001
• 卷：107
• 期：4
• 页码：654-658
• 全文大小：85 K

文摘

Background: Genome and chromosome screens reported DNA markers on chromosome 14 linked to allergic asthma or intermediate phenotypes in several populations. Objective: We sought to perform a linkage study on chromosome 14 and a further association study on candidate genes mapped in the region found to be linked to allergic asthma or intermediate phenotypes. Methods: The study consisted of a sample of 189 families (847 genotyped individuals) from a restricted geographic area in northeastern Italy. The subjects were characterized for the following phenotypes: allergic asthma, total serum IgE levels, skin prick test responses, and bronchial hyperresponsiveness (BHR) to methacholine. Genotyping was done with 14 DNA markers and 4 polymorphisms in the genes encoding α₁-anti-trypsin and α₁-antichymotrypsin (ACT). Results: Multipoint analysis indicated a potential linkage of BHR with marker D14S617 (nonparametric linkage z score = 2.32, P = .01). Transmission disequilibrium of Thr –15Ala in the gene encoding ACT was observed with all the 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. (J Allergy Clin Immunol 2001;107:654-8.)