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 de...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2007
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| _version_ | 1797101154289582080 |
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| author | Abdollahi, MR Lewis, R Gaunt, T Cumming, D Rodriguez, S Rose-Zerilli, M Collins, A Syddall, H Howell, WM Cooper, C Godfrey, K Cameron, I Day, I |
| author_facet | Abdollahi, MR Lewis, R Gaunt, T Cumming, D Rodriguez, S Rose-Zerilli, M Collins, A Syddall, H Howell, WM Cooper, C Godfrey, K Cameron, I Day, I |
| author_sort | Abdollahi, MR |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:47:47Z |
| format | Journal article |
| id | oxford-uuid:e7cc096a-6ab6-4686-90f6-d55f67989ef6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:47:47Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:e7cc096a-6ab6-4686-90f6-d55f67989ef62022-03-27T10:41:46ZQuantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e7cc096a-6ab6-4686-90f6-d55f67989ef6EnglishSymplectic Elements at Oxford2007Abdollahi, MRLewis, RGaunt, TCumming, DRodriguez, SRose-Zerilli, MCollins, ASyddall, HHowell, WMCooper, CGodfrey, KCameron, IDay, IThe 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. |
| spellingShingle | Abdollahi, MR Lewis, R Gaunt, T Cumming, D Rodriguez, S Rose-Zerilli, M Collins, A Syddall, H Howell, WM Cooper, C Godfrey, K Cameron, I Day, I Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits. |
| title | Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits. |
| title_full | Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits. |
| title_fullStr | Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits. |
| title_full_unstemmed | Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits. |
| title_short | Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits. |
| title_sort | quantitated transcript haplotypes qth of agtr1 reduced abundance of mrna haplotypes containing 1166c rs5186 a gt c and relevance to metabolic syndrome traits |
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