β2-adrenoceptor polymorphisms are in linkage disequilibrium, but are not associated with asthma in an adult population

Authors


Dr Hall University Hospital, Nottingham NG7 2UH, UK.

Abstract

Objective

To determine the association between the β2-adrenoceptor polymorphisms at amino acids 16 and 27 and markers of allergic disease and asthma per se in a random adult population, and to determine the degree of linkage disequilibrium existing between polymorphisms at amino acid positions 16, 27, 164 and nucleic acid residue 523.

Methods

We measured serum IgE, skin-prick test positivity, atopy, bronchial hyperreactivity, wheeze and asthma (self-reported and doctor-diagnosed), and determined β2-adrenoceptor genotype by allele specific oligonucleotide hybridization, in 630 adults aged between 18 and 70, selected from the electoral role in a local health authority in Nottingham.

Results

Homozygotes for the Glycine 16 polymorphism had a significantly higher incidence of atopy (χ2 = 6.44 (Pearson's), = 0.04). We also observed a significant association between the Glycine 16 allele and atopy (χ2 = 4.13 (Pearson's), = 0.04), when we assumed the Glycine 16 allele to operate in a dominant mode. No other significant associations between β2-adrenoceptor polymorphisms and markers of allergic disease and asthma per se were observed. Marked linkage disequilibrium exists between the β2-adrenoceptor polymorphisms at amino acid 16 and 27 (D = 0.38, χ2< 0.0001), and between the β2-adrenoceptor polymorphisms at amino acid 27 and nucleic acid residue 523 (C-A) (D = 0.36, χ2< 0.0001).

Conclusion

There is no consistent association between β2-adrenoceptor polymorphisms and the risk of developing allergic disease or asthma per se in this adult sample. Marked linkage disequilibrium exists between the amino acid 16 and 27 polymorphisms, and also between the amino acid 27 polymorphism and the nucleic acid residue 523 (C-A) polymorphism. This polymorphism accounts for the Ban 1 RFLP previously described at the β2-adrenoceptor locus on chromosome 5q 31.

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