| A DEspR T/CATAAAA-box promoter variant decreases DEspR transcription and is associated with increased BP in Sardinian males. | |
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MedLine Citation:
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PMID: 21862670 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Essential hypertension is highly prevalent in the elderly population exceeding 70% in people older than sixty years of age and remains a leading risk factor for heart disease, stroke and chronic renal disease. Elucidation of genetic determinants is critical but remains a challenge due to its complex, multifactorial pathogenesis. We investigated the role DEspR promoter variants, previously associated with male essential hypertension susceptibility, in blood pressure regulation. We detected a single nucleotide polymorphism within the DEspR 5'-regulatory region associated with increased BP in a male Sardinian cohort accounting for 11.0 mmHg of systolic BP (P < 10-15) and 9.3 mmHg of diastolic BP (P < 10(-15)). Sequence analysis of three normotensive subjects homozygous for the rs6535847 "normotension-associated T-allele" identified a canonical TATAAAA-box in contrast to a CATAAAA-motif in three hypertensive subjects homozygous for the rs6535847 "hypertension-associated C-allele". In vitro analysis detected decreased transcription activity with the CATAAAA-motif promoter-construct compared to the canonical TATAAAA-box promoter-construct. Although blood pressure did not differ between DEspR(+/-) knockout male mice and wild-type littermates at 6 months of age, radio-telemetric blood pressure measurements in 18-month old inbred DEspR(+/-) knockout male mice known to have decreased DEspR-RNA and protein, detected higher systolic, mean and diastolic blood pressures in DEspR(+/-) mice compared with littermate wild-type controls (P<0.05). Our results demonstrate that promoter variants in DEspR associated with hypertension susceptibility and increased BP in Sardinian males, affect transcription levels, which then affect blood pressure in an age-dependent and male-specific manner. This finding is concordant with the late-onset and sex-specific characteristics of essential hypertension, thus reiterating the mandate for sex-specific analyses and treatment approaches for essential hypertension. |
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Authors:
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Nicola Glorioso; Victoria L M Herrera; Tamara Didishvili; Giuseppe Argiolas; Chiara Troffa; Patrizia Bulla; Emanuela Bulla; Nelson Ruiz-Opazo |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-23 |
Journal Detail:
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Title: Physiological genomics Volume: - ISSN: 1531-2267 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815683 Medline TA: Physiol Genomics Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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AOU-Universita' di Sassari, Sardinia, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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