Document Detail

Epistatic genetic determinants of blood pressure and mortality in a salt-sensitive hypertension model.
MedLine Citation:
PMID:  19255363     Owner:  NLM     Status:  MEDLINE    
Although genetic determinants protecting against the development of elevated blood pressure (BP) are well investigated, less is known regarding their impact on longevity. We concomitantly assessed genomic regions of rat chromosomes 3 and 7 (RNO3 and RNO7) carrying genetic determinants of BP without known epistasis, for their independent and combinatorial effects on BP and the presence of genetic determinants of survival using Dahl salt-sensitive (S) strains carrying congenic segments from Dahl salt-resistant (R) rats. Although congenic and bicongenic S.R strains carried independent BP quantitative trait loci within the RNO3 and RNO7 congenic regions, only the RNO3 allele(s) independently affected survival. The bicongenic S.R strain showed epistasis between R-rat RNO3 and RNO7 alleles for BP under salt-loading conditions, with less-than-additive effects observed on a 2% NaCl diet and greater-than-additive effects observed after prolonged feeding on a 4% NaCl diet. These RNO3 and RNO7 congenic region alleles had more-than-additive effects on survival. Increased survival of bicongenic compared with RNO3 congenic rats was attributable, in part, to maintaining lower BP despite chronic exposure to an increased dietary salt (4% NaCl) intake, with both strains showing delays in reaching highest BP. R-rat RNO3 alleles were also associated with superior systolic function, with the S.R bicongenic strain showing epistasis between R-rat RNO3 and RNO7 alleles leading to compensatory hypertrophy. Whether these alleles affect survival by additional actions within other BP-regulating tissues/organs remains unexplored. This is the first report of simultaneous detection of independent and epistatic loci dictating, in part, longevity in a hypertensive rat strain.
George T Cicila; Eric E Morgan; Soon Jin Lee; Phyllis Farms; Shane Yerga-Woolwine; Edward J Toland; Ramona S Ramdath; Kathirvel Gopalakrishnan; Keith Bohman; Andrea L Nestor-Kalinoski; Sadik A Khuder; Bina Joe
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-02
Journal Detail:
Title:  Hypertension     Volume:  53     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-20     Completed Date:  2009-04-22     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  725-32     Citation Subset:  IM    
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MeSH Terms
Animals, Congenic
Blood Pressure / genetics*
Cardiomegaly / genetics,  mortality
Disease Models, Animal
Epistasis, Genetic / physiology*
Hypertension / genetics*,  mortality*
Longevity / genetics
Longitudinal Studies
Rats, Inbred Dahl
Sodium Chloride, Dietary / pharmacology
Species Specificity
Survival Analysis
Grant Support
R01 HL020176/HL/NHLBI NIH HHS; R01 HL020176-31/HL/NHLBI NIH HHS; R01 HL020176-32/HL/NHLBI NIH HHS; R01 HL068994-04/HL/NHLBI NIH HHS; R01 HL075414/HL/NHLBI NIH HHS; R01 HL075414-04/HL/NHLBI NIH HHS; R01 HL076709/HL/NHLBI NIH HHS; R01 HL076709-02/HL/NHLBI NIH HHS; R01-HL020176/HL/NHLBI NIH HHS; R01-HL075414/HL/NHLBI NIH HHS; R01-HL68994/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Sodium Chloride, Dietary

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