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Title: Influence of genetic polymorphisms on beta2-adrenoceptor expression and function
Author: Kay, Linda
ISNI:       0000 0001 3595 7994
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2008
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The Pradrenoceptor gene (ADRB2) is polymorphic at a number of loci both within the promoter and coding region. These polymorphisms have been shown to influence both the function and expression of the Beta2-adrenoceptor. However, these findings have been based on studies in transfected cell lines. The aim of the present study was to establish whether polymorphisms in ADRB2 are similarly influential in primary human cell systems. To this end the model system studied was the Beta2-adrenoceptor expressed in human lung mast cells. This study considered single nucleotide polymorphisms (SNPs) and their possible influence on (a) Beta-agonist-mediated responses of mast cells, (b) desensitisation of Beta2adrenoceptor- mediated responses and, (c) expression of the Betap2-adrenoceptor. In addition to individual SNPs, the effect of multiple SNPs (the extended haplotype) on these parameters was also considered. Eleven previously reported polymorphic positions within the ADRB2 were studied for influences of SNPs on Beta2-adrenoceptor function and expression. The only SNPs that influenced (a) p-agonist-mediated responses were 491 C>T (thrI64ile) and -367 T>C, (b) desensitisation of Beta2-adrenoceptor-mediated responses was 46 G>A (glyI6arg) and (c) expression of the P2-adrenoceptor was 491 C>T (thrI64ile). Analysis of multiple SNPs within the ADRB2 indicated that there were three principal extended haplotypes. However, none ofthese haplotypes influenced Beta2-adrenoceptor function or expression. These findings indicate that certain polymorphisms in the ADRB2 influence human pulmonary Pradrenoceptor function and expression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available