Document Detail


Catecholamine pathway gene variation is associated with norepinephrine and epinephrine concentrations at rest and after exercise.
MedLine Citation:
PMID:  22258110     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  22     ISSN:  1744-6880     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-14     Completed Date:  2012-08-01     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  254-60     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
KL2 RR024977/RR/NCRR NIH HHS; KL2 TR000446/TR/NCATS NIH HHS; P01 HL056693/HL/NHLBI 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:
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; X4W3ENH1CV/Norepinephrine; YKH834O4BH/Epinephrine
Comments/Corrections

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