RGD Reference Report - Gender-specific genetic determinants of blood pressure and organ weight: pharmacogenetic approach. - Rat Genome Database

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Gender-specific genetic determinants of blood pressure and organ weight: pharmacogenetic approach.

Authors: Ueno, T  Tremblay, J  Kunes, J  Zicha, J  Dobesova, Z  Pausova, Z  Deng, AY  Sun, Y  Jacob, HJ  Hamet, P 
Citation: Ueno T, etal., Physiol Res 2003;52(6):689-700.
RGD ID: 1303386
Pubmed: PMID:14640890   (View Abstract at PubMed)

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.



Disease Annotations    
Cardiomegaly  (IAGP)
hypertension  (IAGP)
obesity  (IAGP)

Phenotype Annotations    

Objects Annotated

QTLs
Bp259  (Blood pressure QTL 259)
Bp260  (Blood pressure QTL 260)
Bp261  (Blood pressure QTL 261)
Bp262  (Blood pressure QTL 262)
Bp263  (Blood pressure QTL 263)
Bp264  (Blood pressure QTL 264)
Bp265  (Blood pressure QTL 265)
Bp266  (Blood pressure QTL 266)
Bw47  (Body weight QTL 47)
Bw48  (Body weight QTL 48)
Bw49  (Body weight QTL 49)
Bw50  (Body weight QTL 50)
Bw51  (Body weight QTL 51)
Cm38  (Cardiac mass QTL 38)
Cm39  (Cardiac mass QTL 39)
Cm40  (Cardiac mass QTL 40)
Cm41  (Cardiac mass QTL 41)
Cm42  (Cardiac mass QTL 42)
Kidm22  (Kidney mass QTL 22)
Kidm23  (Kidney mass QTL 23)
Kidm24  (Kidney mass QTL 24)
Kidm25  (Kidney mass QTL 25)
Kidm26  (Kidney mass QTL 26)
Kidm27  (Kidney mass QTL 27)
Kidm28  (Kidney mass QTL 28)

Strains
HTG  (Prague hypertriglyceridemic)
LEW  (Lewis)

Objects referenced in this article
QTL Bw39 Body weight QTL 39 Rattus norvegicus
Strain LEW/Cub null Rattus norvegicus

Additional Information