Linkage between IgE receptor-mediated histamine releasability from basophils and gene marker of chromosome 11q13

Background: The genetics of the regulation of the release of mediators involving the interaction of IgE with cells and their ability to release mediators have not been extensively investigated. With use of the candidate gene approach, it was reported that the gene regulating the β chain of the high-affinity receptor for IgE is on chromosome 11ql3. Objective: To determine whether gene(s) in chromosome 11ql3 may control the expression of maximal histamine release from basophil to anti-IgE stimuli, linkage analysis between this phenotype and the gene marker of chromosome 11ql3 was performed. Methods: Maximal histamine release to anti-IgE and calcium ionophore A23187 and genotyping chromosome 11ql3 with use of microsatellite marker (D11S97) were performed in 56 probands with asthma and 59 of their siblings. The linkage was analyzed by affected sib-pair analysis and the quantitative trait locus approach. Results: Maximal histamine release (mean ± SE) to anti-IgE and A23187 was 43.3% ± 3.5% and 30.9 ± 3.4% in probands and 29.5% ± 2.6% and 22.2% ± 2.7 in siblings, respectively. Of 20 sib-pairs with the maximal histamine release to anti-IgE more than 33% (mean plus 1 SD of nonasthmatic controls), 11 (55%) shared 2 D11S97 alleles, 9 (45%) shared 1 allele, and neither sib-pair shared identical alleles, which indicates a significant linkage of maximal histamine to anti-IgE and gene marker of chromosome 11ql3 (P = .02). The difference (mean ± SE) of the maximal histamine release to anti-IgE between each proband and sibling was smaller in sib-pairs with 2 identical alleles than in those with 1 identical allele and with no identical allele (14.1% ± 2.6% vs 25.8% ± 3.1% vs 41.0% ± 4.9%). However, the difference (mean ± SE) to A23187 between each proband and sibling was not different among the 3 groups (9.7% ± 1.8% vs 17.9% ± 3.6% vs 10.4% ± 4.8%). Conclusion: Maximal histamine release from basophils to anti-IgE stimuli was linked to the gene marker of chromosome 11ql3.