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Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits

Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits
Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits
The angiotensin II type 1 receptor (AGTR1) is the main target through which angiotensin II influences cardiovascular tone, cell growth, and fluid and electrolyte balance. AGTR1 polymorphism has been reported to associate with hypertension, myocardial infarction (MI), and metabolic traits. Here we describe a novel approach to quantitation of transcript haplotypes (QTH) of AGTR1. To determine relative allelic expression from haplotypes, within-individual-between-allele ratiometric analyses in placental cDNA were developed for the transcribed SNPs rs5182:C>T (encoding p.L191) and rs5186:A>C (3?-noncoding “A1166C”). Additionally, between-individual comparisons were made using TaqMan® assays applied to both homozygous and heterozygous genotypes and haplotypes. In conjunction, linkage disequilibrium (LD) and genomic haplotype associations with metabolic syndrome were examined. There was no significant difference of mRNA level for alleles of rs5182:C>T, but allele and mRNA haplotypes carrying 1166C exhibited reduced abundance. The effect was much greater in CC homozygotes than in heterozygotes. The promoter region was confirmed to be in a separate haplotype block from the AGTR1 3? region containing rs5182:C>T and rs5186:A>C. Metabolic syndrome trait associations were strongest for the 3? block generally and for the C allele of rs5186:A>C specifically. All effects were much more prominent in homozygotes, possibly reflecting interallelic interaction through feedback loops of mRNA regulation. Differential abundance of AGTR1 mRNA haplotypes may mediate clinical phenotypic observations of the AGTR1 genotype.
ngiotensin II type 1 receptor, AGTR1, haplotype, gene expression, insertion deletion, angiotensin converting enzyme, ACE
1059-7794
365-373
Abdollahi, Mohammad R.
96ec68db-6302-4216-9aaf-9951a44be8b8
Lewis, Rohan M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Gaunt, Tom R.
ff4bc39d-405c-4ba1-896b-7e7d2f747387
Cumming, Debbie V.E.
46772d63-3614-44fc-9ac2-0d71025a6ce9
Rodriguez, Santiago
f235ea2b-b6f3-45e4-9fc3-5a0383689ed6
Rose-Zerilli, Matthew
dc2a6ac8-f8e6-4604-b108-948477c8e043
Collins, Andrew R.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Syddall, Holly E.
a0181a93-8fc3-4998-a996-7963f0128328
Howell, William M.
1c09187d-f560-4432-badc-08c1270ac79d
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Cameron, Iain T.
f7595539-efa6-4687-b161-e1e93ff710f2
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39
Abdollahi, Mohammad R.
96ec68db-6302-4216-9aaf-9951a44be8b8
Lewis, Rohan M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Gaunt, Tom R.
ff4bc39d-405c-4ba1-896b-7e7d2f747387
Cumming, Debbie V.E.
46772d63-3614-44fc-9ac2-0d71025a6ce9
Rodriguez, Santiago
f235ea2b-b6f3-45e4-9fc3-5a0383689ed6
Rose-Zerilli, Matthew
dc2a6ac8-f8e6-4604-b108-948477c8e043
Collins, Andrew R.
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Syddall, Holly E.
a0181a93-8fc3-4998-a996-7963f0128328
Howell, William M.
1c09187d-f560-4432-badc-08c1270ac79d
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Cameron, Iain T.
f7595539-efa6-4687-b161-e1e93ff710f2
Day, Ian N.M.
b749b30a-1f4c-40eb-af0e-a50427388b39

Abdollahi, Mohammad R., Lewis, Rohan M., Gaunt, Tom R., Cumming, Debbie V.E., Rodriguez, Santiago, Rose-Zerilli, Matthew, Collins, Andrew R., Syddall, Holly E., Howell, William M., Cooper, Cyrus, Godfrey, Keith M., Cameron, Iain T. and Day, Ian N.M. (2007) Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits. Human Mutation, 28 (4), 365-373. (doi:10.1002/humu.20454). (PMID:17211857)

Record type: Article

Abstract

The angiotensin II type 1 receptor (AGTR1) is the main target through which angiotensin II influences cardiovascular tone, cell growth, and fluid and electrolyte balance. AGTR1 polymorphism has been reported to associate with hypertension, myocardial infarction (MI), and metabolic traits. Here we describe a novel approach to quantitation of transcript haplotypes (QTH) of AGTR1. To determine relative allelic expression from haplotypes, within-individual-between-allele ratiometric analyses in placental cDNA were developed for the transcribed SNPs rs5182:C>T (encoding p.L191) and rs5186:A>C (3?-noncoding “A1166C”). Additionally, between-individual comparisons were made using TaqMan® assays applied to both homozygous and heterozygous genotypes and haplotypes. In conjunction, linkage disequilibrium (LD) and genomic haplotype associations with metabolic syndrome were examined. There was no significant difference of mRNA level for alleles of rs5182:C>T, but allele and mRNA haplotypes carrying 1166C exhibited reduced abundance. The effect was much greater in CC homozygotes than in heterozygotes. The promoter region was confirmed to be in a separate haplotype block from the AGTR1 3? region containing rs5182:C>T and rs5186:A>C. Metabolic syndrome trait associations were strongest for the 3? block generally and for the C allele of rs5186:A>C specifically. All effects were much more prominent in homozygotes, possibly reflecting interallelic interaction through feedback loops of mRNA regulation. Differential abundance of AGTR1 mRNA haplotypes may mediate clinical phenotypic observations of the AGTR1 genotype.

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e-pub ahead of print date: 8 January 2007
Published date: April 2007
Keywords: ngiotensin II type 1 receptor, AGTR1, haplotype, gene expression, insertion deletion, angiotensin converting enzyme, ACE
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 44211
URI: https://eprints.soton.ac.uk/id/eprint/44211
ISSN: 1059-7794
PURE UUID: 257667c0-dbcf-44ef-81ac-bb17cd1f32c6
ORCID for Rohan M. Lewis: ORCID iD orcid.org/0000-0003-4044-9104
ORCID for Andrew R. Collins: ORCID iD orcid.org/0000-0001-7108-0771
ORCID for Holly E. Syddall: ORCID iD orcid.org/0000-0003-0171-0306
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Keith M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Iain T. Cameron: ORCID iD orcid.org/0000-0002-4875-267X

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Date deposited: 21 Feb 2007
Last modified: 14 Mar 2019 01:54

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Contributors

Author: Rohan M. Lewis ORCID iD
Author: Tom R. Gaunt
Author: Debbie V.E. Cumming
Author: Santiago Rodriguez
Author: Matthew Rose-Zerilli
Author: William M. Howell
Author: Cyrus Cooper ORCID iD
Author: Iain T. Cameron ORCID iD
Author: Ian N.M. Day

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