Linkage between bronchial responsiveness to methacholine and gene markers of IL-4 cytokine gene cluster and T-cell receptor alpha/delta gene complex in Korean nuclear families

Background Several candidate genes have been reported to be linked to inter mediate phenotypes of asthma in Caucasian populations. Objective To evaluate linkage between phenotypes of asthma and gene markers of high affinity IgE receptor-beta gene (D11S97), IL-4 cytokine gene clust er (IL-4R1), and T-cell receptor alpha/delta gene complex (D14S50) in Korea n nuclear families. Methods Nuclear families (127 probands and their 130 siblings) for the link age analysis were ascertained through asthmatic children. Linkages between total serum IgE response, skin responses to common aeroallergens, and bronc hial responsiveness to methacholine were performed using a sib-pair approac h. Results The square difference of the slope of the dose-response curve (DRS) between sib-pairs with two IL-4R1 identical alleles was smaller than with one or with neither lL-4R1 identical allele (P = 0.004). As for D14S50, the differences of DRS between sib-pairs with two identical alleles and with o ne identical allele were smaller than with neither identical alleles (P = 0 .01). As for D11S97, no significant differences were observed among the gro ups with identical alleles of two, one or zero. With regard to total serum IgE levels, no significant linkage was found between this phenotype and the above three gene markers. As for skin responses to common aeroallergens, s ignificant evidence was obtained to establish a linkage between this phenot ype and the marker IL-4R1 (P = 0.01). However, no significant linkage was f ound between this phenotype and the markers D11S97 and D14S50. Conclusion The expression of bronchial responsiveness to methacholine may b e influenced by genetic factors in the IL-4 cytokine gene cluster and/or T- cell receptor alpha/delta gene complex, but the genetic influence of the Fc epsilon RI-beta gene may be minimal in the expression of bronchial respons iveness in Korean nuclear families.