Exclusion of chromosome 11q and the Fc∊RI-β gene as aetiological factors in allergy and asthma in a population of Dutch asthmatic families

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Abstract

Background

The β subunit of the high-affinity receptor for IgE (Fc∊RI-β) is localized to chromosome 11q13 and has been reported by Cookson et al. to be in close genetic linkage with a gene for atopy. A maternally inherited association was found between the presence of a variant of Fc∊RI-β, Ile181Leu, and high total serum IgE levels (IgE > 100IU). In a previous study of 20 Dutch families, we found no evidence for linkage of atopy or bronchial hyperresponsiveness (BHR) to chromosome 11q.

Objective

Recently segregation analysis in 92 families has given us evidence for two independent major loci accounting for 78% of the observed variance in total serum IgE levels, and linkage analysis using both sib-pair and LOD score methods has identified one major locus for regulation of IgE levels and BHR near the cytokine gene complex on chromosome 5q. The objective of this study is to pursue the identification of the second major locus.

Methods

We have studied markers in the area of the high affinity IgE receptor (Fc∊RI-β) on chromosome 11q (D11S1314, Fc∊RI-β and D11S987) in 83 families for whom DNA was available. Furthermore, our families have been examined for variance in the Fc∊RI-β gene, specifically for Leu181 and Leu181/Leu183 mutations.

Results

By sib-pair analysis, there is no evidence for linkage of total serum IgE levels or number of positive skin tests to these markers in our population. Similar negative results were obtained for affected sib-pair analysis of BHR, with the exception of D11S1314, which was significant at P = 0.046. The Fc∊R1-β gene in 36 female probands, 44 male probands and 46 female spouses was sequenced for these mutations. For each of these 126 individuals sequencing of Fc∊RI-β demonstrated a wild-type sequence pattern, with no mutations found in anyone, male or female.

Conclusion

We are unable to confirm the presence of significant mutations in Fc∊R1-β gene in our population, and we cannot confirm that the Fc∊R1-β gene is crucial to the pathogenesis of allergic inflammation in asthma.

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