Gender-specific genetic determinants of blood pressure and organ weight: pharmacogenetic approach. Physiol Res 2003;52(6):689-700
Date
12/04/2003Pubmed ID
14640890Scopus ID
2-s2.0-0346500572 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
A total genome scan and pharmacogenetic study were designed to search for genetic determinants of blood pressure (BP) as well as heart and kidney weights. Genome scanning was carried out in 266 F(2) intercrosses from Prague hypertensive hypertriglyceridemic rats for phenotypes of organ weights, baseline BP, BP after blockade of the renin-angiotensin system (RAS) by losartan, of the sympathetic nervous system (SNS) by pentolinium, and of the nitric oxide (NO) synthase by N(G)-nitro-L-arginine methyl ester. Pharmacogenetic analysis showed that, in males, BP was controlled by two loci on chromosomes 1 and 5 (Chr1, Chr5) through the SNS, and these loci showed a positive contribution for relative kidney weight (KW/BW). On the other hand, baseline BP in females was controlled by two loci on Chr3 and Chr7. The effect of these loci was not mediated by the RAS, SNS or NO system. These loci did not show any effect for KW/BW. Negatively-linked loci for KW/BW and relative heart weight (HW/BW) were identified on Chr2 in both genders. Another negatively-linked locus for KW/BW, located on Chr8 in males, affected BP through the SNS. This locus on Chr8 overlapped with a previously-reported modifier locus for polycystic kidney disease (PKD). In conclusion, this pharmacogenetic study determined two loci for BP and relative organ mass implicating sympathetic overactivity. Concordance of the identified locus for KW/BW and BP through the SNS on Chr8 with the PKD locus revealed the importance of this region for renal complications in various diseases.
Author List
Ueno T, Tremblay J, Kunes J, Zicha J, Dobesová Z, Pausova Z, Deng AY, Sun Y, Jacob HJ, Hamet PMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Body Weight
Chromosomes, Mammalian
Crosses, Genetic
Disease Models, Animal
Female
Genotype
Heart
Hypertension
Kidney
Lod Score
Losartan
Male
Microvascular Angina
Multifactorial Inheritance
NG-Nitroarginine Methyl Ester
Organ Size
Pentolinium Tartrate
Pharmacogenetics
Phenotype
Polymorphism, Genetic
Quantitative Trait Loci
Rats
Rats, Inbred Lew
Rats, Wistar
Sex Factors
