Details

Autor(en) / Beteiligte

• Dewar, Jane C

Titel

The contribution of genetic variation within the #beta#←2 adrenoceptor and the h←1 receptor to asthma and markers of allergic disease

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

1999

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• The genes encoding the 2 adrenoceptor and the H1 receptor are potentially important candidate genes given that these receptors are major therapeutic targets. The contribution of genetic variation within these receptor to asthma and the allergic diathesis has therefore been examined in this thesis:In this thesis, the prevalence of the two functionally relevant non-degenerate polymorphisms at loci 16 and 27 has been established in a large family (n=324) and random adult sample (n=630). Both occur commonly in each population with the following approximate allelic frequencies: Arg 16 40%, Gly 16 60%, Gln 27 50%, Glu 27 50%. The extent of linkage disequilibrium within the 2 adrenoceptor locus has been determined between the amino acid 16, 27, 164 and codon 523 polymorphisms. Amino acids 16 and 27 are in tight linkage disequilibrium with one another (D=0.38, P<0.0001), and also with codon 523 (D=0.39, P<0.0001, D=0.36, P<0.001 respectively). The contribution of the two common polymorphisms at locus 16 and 27 (Arg-Gly 16, Gln-Glu 27) to the development and expression of asthma has also been determined in these samples . Whilst the Gln 27 wild-type form of receptor was significantly associated with total IgE (p=0.009), with significant linkage (r=0.24, p=0.037), in the family sample, this result could not be replicated in the random adult sample. No positive associations were seen between each locus and asthma and its other intermediate phenotypes, BHR or atopy.In comparison to the 2 adrenoceptor, the molecular genetics of the H1 receptor are poorly understood to date. The open-reading frame of the gene was screened for polymorphisms using the technique of SSCP. A single degenerate polymorphism at codon 356 was identified with a frequency of 3.8%. No other polymorphisms were detected. These results suggest that the 2 adrenoceptor and the H1 receptor do not represent major genetic loci in asthma or atopy.