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Genetic studies of the Renin Angiotensin pathway genes and quantitative studies of transcribed haplotypes of the angiotensin II type I receptor gene

Genetic studies of the Renin Angiotensin pathway genes and quantitative studies of transcribed haplotypes of the angiotensin II type I receptor gene
Genetic studies of the Renin Angiotensin pathway genes and quantitative studies of transcribed haplotypes of the angiotensin II type I receptor gene

We have studied the association of the AGTR1 A1166C with cardiovascular and metabolic traits in the north and east Hertfordshire UK populations.  The results represent that CC genotype is a strong determinant of anthropometric measures in men and also shows associations with traits of insulin resistance.  Another SNP (L191L) in exon 5 and two more (C-521T and A-153G) in the 5’UTR have also been typed to resolve the structure of haplotype blocks in the AGTR1.  The possible association of these SNPs with the above phenotypes was also studied.  L191L, to a lesser extent, was also significantly associated with some of the above phenotypes.  C-521T and A-153G has much less strong association.  However, there were some associations in haplotype phenotype study.  It was found that there are two main haplotype blocks separated by a gap in the AGTR1 gene.

There are also association between GH polymorphisms (A5157G, C5187A and microsatellite) and metabolic traits.  Therefore a study was undertaken of linkage disequilibrium (LD) between these polymorphisms and those of the ACE gene (A5466C, C1237T and I/D).  This study showed that there are relatively significant levels of LD between the above polymorphisms.  Detailed haplotype analysis has been undertaken in the ACE gene, and haplotype frequencies accord well with published literature.  The AGT M235T was also typed and studied in the NH and EH populations, but no significant association was observed.

To examine the functional effects of the AGTR1 A1166C and L191L polymorphisms, a ratiometric analysis was developed to compare the ratio of band intensities following restriction digestion of cDNA derived from L191L and A1166C heterozygotes.  Additional to these, within-individual-between-allele assays and between-individual comparisons were made using TaqMan assays applied to both homozygous and heterozygous genotype and haplotype.  No significant effect appeared from alleles of the L191L, but the C allele of the A1166C and haplotypes carrying it downregulated the AGTR1 mRNA.

University of Southampton
Abdollahi, Mohammad Reza
dbae8211-c11f-463f-b5ed-cea609f9cbc7
Abdollahi, Mohammad Reza
dbae8211-c11f-463f-b5ed-cea609f9cbc7

Abdollahi, Mohammad Reza (2004) Genetic studies of the Renin Angiotensin pathway genes and quantitative studies of transcribed haplotypes of the angiotensin II type I receptor gene. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

We have studied the association of the AGTR1 A1166C with cardiovascular and metabolic traits in the north and east Hertfordshire UK populations.  The results represent that CC genotype is a strong determinant of anthropometric measures in men and also shows associations with traits of insulin resistance.  Another SNP (L191L) in exon 5 and two more (C-521T and A-153G) in the 5’UTR have also been typed to resolve the structure of haplotype blocks in the AGTR1.  The possible association of these SNPs with the above phenotypes was also studied.  L191L, to a lesser extent, was also significantly associated with some of the above phenotypes.  C-521T and A-153G has much less strong association.  However, there were some associations in haplotype phenotype study.  It was found that there are two main haplotype blocks separated by a gap in the AGTR1 gene.

There are also association between GH polymorphisms (A5157G, C5187A and microsatellite) and metabolic traits.  Therefore a study was undertaken of linkage disequilibrium (LD) between these polymorphisms and those of the ACE gene (A5466C, C1237T and I/D).  This study showed that there are relatively significant levels of LD between the above polymorphisms.  Detailed haplotype analysis has been undertaken in the ACE gene, and haplotype frequencies accord well with published literature.  The AGT M235T was also typed and studied in the NH and EH populations, but no significant association was observed.

To examine the functional effects of the AGTR1 A1166C and L191L polymorphisms, a ratiometric analysis was developed to compare the ratio of band intensities following restriction digestion of cDNA derived from L191L and A1166C heterozygotes.  Additional to these, within-individual-between-allele assays and between-individual comparisons were made using TaqMan assays applied to both homozygous and heterozygous genotype and haplotype.  No significant effect appeared from alleles of the L191L, but the C allele of the A1166C and haplotypes carrying it downregulated the AGTR1 mRNA.

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Published date: 2004

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Local EPrints ID: 465465
URI: http://eprints.soton.ac.uk/id/eprint/465465
PURE UUID: d8d30bc9-ca1c-4794-8602-35bb02df4e45

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Date deposited: 05 Jul 2022 01:12
Last modified: 16 Mar 2024 20:12

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Author: Mohammad Reza Abdollahi

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