| Catecholamine pathway gene variation is associated with norepinephrine and epinephrine concentrations at rest and after exercise. | |
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MedLine Citation:
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PMID: 22258110 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To examine the hypothesis that genetic variation in enzymes and transporters associated with synthesis, storage, release, and metabolism of catecholamines contributes to the interindividual variability in plasma catecholamine concentrations at rest and after exercise. METHODS: We measured plasma norepinephrine (NE) and epinephrine concentrations at rest and after a standardized exercise protocol in 165 healthy individuals (60% White, 40% African-American) and examined 29 functional or common variants in 14 genes involved in synthesis, transport, or metabolism of catecholamines. We examined the relationship between genotypes and NE concentrations at rest and the increase after exercise (ΔNE) by multiple linear regression with adjustment for covariates [age, race, sex, BMI, fitness, and resting NE (for ΔNE)]. As a secondary outcome, we carried out similar analyses for epinephrine concentrations. RESULTS: There was large interindividual variability in resting NE (mean, 204±102 pg/ml; range, 39-616 pg/ml) and ΔNE (mean, 256±206 pg/ml; range, -97 to 953 pg/ml). Resting NE was significantly associated with variants of four genes: CYB561 (P<0.001), VMAT2 (P=0.016), CHGA (P=0.039), and PNMT (P=0.038). ΔNE after exercise was associated with three variants of PNMT (P=0.041) and COMT (P=0.033 and 0.035), and resting and exercise epinephrine concentrations were associated with two variants each. CONCLUSION: The findings of this exploratory study suggest that variation in catecholamine pathway genes contributes to the interindividual variability in plasma NE and epinephrine concentrations at rest and after exercise. |
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Authors:
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Laxmi V Ghimire; Utkarsh Kohli; Chun Li; Gbenga G Sofowora; Mordechai Muszkat; Eitan A Friedman; Joseph F Solus; Alastair J J Wood; C Michael Stein; Daniel Kurnik |
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: 22 ISSN: 1744-6880 ISO Abbreviation: Pharmacogenet. Genomics Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-03-14 Completed Date: 2012-08-01 Revised Date: 2013-05-22 |
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: 254-60 Citation Subset: IM |
Affiliation:
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Department of Medicine, Division of Clinical, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult African Continental Ancestry Group / genetics Catecholamines / biosynthesis, genetics*, metabolism Chromogranin A / genetics Clinical Trials as Topic Cytochrome b Group / genetics Epinephrine / blood* European Continental Ancestry Group / genetics Exercise / physiology Female Genetic Association Studies Genotype Humans Male Metabolic Networks and Pathways* Norepinephrine / blood* Rest / physiology Tumor Suppressor Proteins / genetics Vesicular Monoamine Transport Proteins / genetics |
| Grant Support | |
ID/Acronym/Agency:
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KL2 RR024977/RR/NCRR NIH HHS; KL2 TR000446/TR/NCATS NIH HHS; P01 HL056693-14/HL/NHLBI NIH HHS; P01 HL56693/HL/NHLBI NIH HHS; TL1 RR024978/RR/NCRR NIH HHS; TL1 TR000447/TR/NCATS NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 RR024975/RR/NCRR NIH HHS; UL1 RR024975-05/RR/NCRR NIH HHS; UL1 TR000445/TR/NCATS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CHGA protein, human; 0/CYB561D2 protein, human; 0/Catecholamines; 0/Chromogranin A; 0/Cytochrome b Group; 0/SLC18A2 protein, human; 0/Tumor Suppressor Proteins; 0/Vesicular Monoamine Transport Proteins; 51-41-2/Norepinephrine; 51-43-4/Epinephrine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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