1. Physiol Genomics. 2006 Aug 16;26(3):172-9. Epub 2006 May 23.
Sex-specific QTLs and interacting loci underlie salt-sensitive hypertension and
target organ complications in Dahl S/jrHS hypertensive rats.
Herrera VL(1), Tsikoudakis A, Ponce LR, Matsubara Y, Ruiz-Opazo N.
Author information:
(1)Section of Molecular Medicine, Department of Medicine, and Whitaker
Cardiovascular Institute, Boston University School of Medicine, Boston,
Massachusetts 02118, USA.
Sex-specific differences in polygenic (essential) hypertension are commonly
attributed to the role of sex steroid hormone-receptor systems attenuating
sex-common disease mechanisms in premenopausal women. However, emerging
observations indicate sex-specific genetic susceptibility in various traits, thus
requiring systematic study. Here we report a comparative analysis of independent
total genome scans for salt-sensitive hypertension susceptibility quantitative
trait loci (QTLs) in male and female F2 [Dahl R/jrHS x S/jrHS] intercross rats
exposed to high-salt (8% NaCl) rat diets. Hypertension was phenotyped with three
quantitative traits: blood pressure (BP) elevation associated with increased
hypertensive renal disease [glomerular injury score (GIS)] and increased cardiac
mass [relative heart weight (RHW)] obtained 8-12 wk after high-salt challenge;
24-h nonstress, telemetric BP measurements were used. Although sex-common QTLs
were detected for BP [chromosome (chr) 1-144.3 Mbp; chr 1-208.8 Mbp], GIS (chr
1-208.8 Mbp), and cardiac mass (chr 5-150.3 Mbp), most QTLs across the three
phenotypes studied are gender specific as follows: female QTLs for BP (chr
2-106.7 Mbp, chr 2-181.7 Mbp, chr 5-113.9 Mbp, chr 5-146.7 Mbp, chr 12-12.8 Mbp),
GIS (chr 15-59.6 Mbp), and RHW (chr 2-31.5 Mbp, chr 5-154.7 Mbp, chr 5-110.9
Mbp); male QTLs for BP (chr 2-196.7 Mbp, chr 11-48.0 Mbp, chr 20-35.7 Mbp), GIS
(chr 6-3.3 Mbp, chr 20-40.7 Mbp), and RHW (chr 6-3.3 Mbp, chr 20-40.7 Mbp).
Furthermore, interacting loci with significant linkage were detected only in
female F2 intercross rats for BP and hypertensive renal disease. Comparative
analyses revealed concordance of BP QTL peaks with previously reported rat model
and human hypertension susceptibility genes and with BP QTLs in previous Dahl
S-derived F2 intercross studies and also suggest strain-specific genetic
modifiers of sex-specific determinants. Altogether, the data provide key
experimental bases for sex-specific investigation of mechanisms and intervention
and prevention strategies for polygenic hypertension in humans.
PMID: 16720678 [PubMed - indexed for MEDLINE]
PUBMED: 16720678
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