Document Detail


Genetic variants in the alpha2C-adrenoceptor and G-protein contribute to ethnic differences in cardiovascular stress responses.
MedLine Citation:
PMID:  18698227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Cardiovascular responses to stressors are regulated by sympathetic activity, increased in black Americans, and associated with future cardiovascular morbidity. Our aim was to determine whether two functional variants in genes regulating sympathetic activity, a deletion in the alpha2C-adrenergic receptor (ADRA2C del322-325) and a G-protein beta3-subunit variant (GNB3 G825T), affect cardiovascular responses to physiologic stressors and contribute to their ethnic differences.
METHODS: We measured heart rate and blood pressure responses to a cold pressor test (CPT) in 79 healthy participants (40 blacks, 39 whites), aged 25.7+/-5.3 years, and determined genotypes for the ADRA2C and GNB3 variants. We examined the response variables (increase in heart rate and blood pressure) in multiple linear regression analyses adjusting first for baseline measures, ethnicity, and other covariates, and then additionally for genotypes.
RESULTS: Black participants had a greater heart rate response to CPT than whites [mean difference, 9.9 bpm; 95% confidence interval (CI), 4.1 to 15.6; P=0.001]. Both the ADRA2C del/del (15.8 bpm; 95% CI, 8.0-23.7; P<0.001) and GNB3 T/T genotypes (6.8 bpm; 95% CI, 0.9-12.7; P=0.026) were associated with greater heart rate response. After adjusting for genotypes, the ethnic difference was abrogated (1.3 bpm; 95% CI, -5.4-8.0; P=0.70), suggesting that the genetic variants contributed substantially to ethnic differences.
CONCLUSION: Variation in genes that regulate sympathetic activity affects hemodynamic stress responses and contributes to their ethnic differences. This study elucidates how genetic factors may in part explain ethnic differences in cardiovascular regulation.
Authors:
Daniel Kurnik; Eitan A Friedman; Mordechai Muszkat; Gbenga G Sofowora; Hong-Guang Xie; William D Dupont; Alastair J J Wood; C Michael Stein
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  18     ISSN:  1744-6872     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-13     Completed Date:  2008-10-03     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  743-50     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
African Continental Ancestry Group / genetics*
Blood Pressure / physiology
Cardiovascular System / physiopathology*
Catecholamines / metabolism
Cold Temperature
European Continental Ancestry Group / genetics*
Female
Genetic Variation / genetics*
Genotype
Heart Rate
Heterotrimeric GTP-Binding Proteins / genetics*
Humans
Male
Protein Subunits
Receptors, Adrenergic, alpha-2 / genetics*
Stress, Psychological / genetics*
Grant Support
ID/Acronym/Agency:
GM 31304/GM/NIGMS NIH HHS; M01 RR 00095/RR/NCRR NIH HHS; M01 RR000095/RR/NCRR NIH HHS; M01 RR000095-420654/RR/NCRR NIH HHS; P01 GM031304-200021/GM/NIGMS NIH HHS; P01 HL 56693/HL/NHLBI NIH HHS; P01 HL056693/HL/NHLBI NIH HHS; P01 HL056693-03/HL/NHLBI NIH HHS; U01 HL 65962/HL/NHLBI NIH HHS; U01 HL065962/HL/NHLBI NIH HHS; U01 HL065962-08/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/ADRA2C protein, human; 0/Catecholamines; 0/G-protein beta3 subunit; 0/Protein Subunits; 0/Receptors, Adrenergic, alpha-2; EC 3.6.5.1/Heterotrimeric GTP-Binding Proteins
Comments/Corrections

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