ASTHMA

Linkage/association study of a locus modulating total serum IgE on chromosome 14q13–24 in families with asthma

A H Mansur¹, D T Bishop², S T Holgate³, A F Markham⁴, J F J Morrison (deceased)⁵

¹ Respiratory Department, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK
² ICRF, Genetic Epidemiology Laboratory, St James’s University Hospital, Leeds, UK
³ Medical Specialities (RCMB), Southampton General Hospital, Southampton, UK
⁴ Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James’s University Hospital, Leeds, UK
⁵ AstraZeneca, Macclesfield, Cheshire, UK

Correspondence to:
Correspondence to:
Dr A H Mansur
Respiratory Department, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK; adel.mansur{at}heartsol.wmids.nhs.uk

Background: A study was undertaken to validate a locus modulating total serum IgE levels on 14q13–24.

Methods: A linkage and association study was performed between total serum IgE and a panel of seven microsatellites which map to the 14q13–24 region in 69 families with asthma recruited from Leeds, UK.

Results: Non-parametric, multipoint, sib pair analysis showed no evidence of genetic linkage between the quantitative trait "log IgE" and any of the tested markers. However, a significant association was observed between locus D14S63 (14q23) and total serum IgE (p = 0.017). Allelic analysis showed an association between low total IgE and allele 157 of D14S63 (p = 0.01, OR = 0.63, 95% CI 0.44 to 0.90). Modelling of allele 157 genotypes as a continuous covariate indicated evidence of a significant inverse linear trend across the three genotypes where 157 homozygotes had the lowest mean log IgE (p = 0.045). Association of D14S63 with log IgE was confirmed in the analysis of a combined dataset of 53 families from Southampton, UK and the 69 families from Leeds (total 122 families). An association was observed at the locus level (p = 0.022) and the allelic level where allele 165 showed an association with high total IgE (p = 0.001, OR = 3.79, 95% CI 1.54 to 9.7) and allele 157 showed an association with low total IgE (p = 0.041, OR = 0.77, 95% CI 0.6 to 0.99). The transmission disequilibrium test was positive for allele 165 (p<0.05) and negative for allele 157 (p>0.05).

Conclusions: Despite the lack of linkage, the findings of this study support the previous observation of a gene(s) at 14q23 that modulates total serum IgE.

Keywords: IgE; asthma; genetics

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