| Genetic variation in the presynaptic norepinephrine transporter is associated with blood pressure responses to exercise in healthy humans. | |
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MedLine Citation:
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PMID: 21412203 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The presynaptic norepinephrine transporter (NET) mediates synaptic clearance and recycling of norepinephrine. NET-deficient transgenic mice have elevated blood pressure (BP), heart rate, and catecholamine concentrations. However, the in-vivo effects of common NET variants on cardiovascular regulation at rest and during exercise are unknown. METHODS: We studied cardiovascular responses and plasma catecholamine concentrations at rest and during bicycle exercise at increasing workloads (25, 50, and 75 W) in 145 healthy participants. We used multiple linear regressions to analyze the effect of common, purportedly functional polymorphisms in NET (rs2242446 and rs28386840) on cardiovascular measures. RESULTS: 44 and 58.9% of participants carried at least one variant allele for NET T-182C and A-3081T, respectively. Systolic BP during exercise and systolic BP-area under the curve were higher in carriers of variant NET alleles (P=0.003 and 0.009 for T-182C and A-3081T, respectively) and NET haplotype -182C/-3081T compared with -182T/-3081A (all P<0.01). Diastolic BP during exercise was also higher at lower, but not at higher exercise stages in carriers of NET -182C (P<0.01) and -3081T variants (P<0.05). NET genotypes were not associated with catecholamine concentrations or heart rate. CONCLUSION: Common genetic NET variants (-182C and -3081T) are associated with greater BP response to exercise in humans. |
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Authors:
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Utkarsh Kohli; Maureen K Hahn; Brett A English; Gbenga G Sofowora; Mordechai Muszkat; Chun Li; Randy D Blakely; C Michael Stein; Daniel Kurnik |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Pharmacogenetics and genomics Volume: 21 ISSN: 1744-6880 ISO Abbreviation: Pharmacogenet. Genomics Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-17 Completed Date: 2011-07-22 Revised Date: 2012-04-04 |
Medline Journal Info:
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Nlm Unique ID: 101231005 Medline TA: Pharmacogenet Genomics Country: United States |
Other Details:
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Languages: eng Pagination: 171-8 Citation Subset: IM |
Affiliation:
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Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Blood Pressure / genetics* Catecholamines / blood Cohort Studies Exercise / physiology* Female Genetic Variation* Genotype Humans Male Middle Aged Norepinephrine / metabolism* Norepinephrine Plasma Membrane Transport Proteins / genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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1 UL 1 RR024975/RR/NCRR NIH HHS; GM31304/GM/NIGMS NIH HHS; P01 GM031304-23/GM/NIGMS NIH HHS; P01 HL056693-14/HL/NHLBI NIH HHS; P01 HL56693/HL/NHLBI NIH HHS; U01 HL065962-09/HL/NHLBI NIH HHS; U01 HL65962/HL/NHLBI NIH HHS; UL1 RR024975-05/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Catecholamines; 0/Norepinephrine Plasma Membrane Transport Proteins; 51-41-2/Norepinephrine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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