RGD Reference Report - Sex-specific QTLs and interacting loci underlie salt-sensitive hypertension and target organ complications in Dahl S/jrHS hypertensive rats. - Rat Genome Database

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Sex-specific QTLs and interacting loci underlie salt-sensitive hypertension and target organ complications in Dahl S/jrHS hypertensive rats.

Authors: Herrera, VL  Tsikoudakis, A  Ponce, LR  Matsubara, Y  Ruiz-Opazo, N 
Citation: Herrera VL, etal., Physiol Genomics. 2006 Aug 16;26(3):172-9. Epub 2006 May 23.
RGD ID: 1581737
Pubmed: PMID:16720678   (View Abstract at PubMed)
DOI: DOI:10.1152/physiolgenomics.00285.2005   (Journal Full-text)

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.

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Objects Annotated

QTLs
Bp287  (Blood pressure QTL 287)
Bp288  (Blood pressure QTL 288)
Bp289  (Blood pressure QTL 289)
Bp290  (Blood pressure QTL 290)
Bp291  (Blood pressure QTL 291)
Bp292  (Blood pressure QTL 292)
Bp293  (Blood pressure QTL 293)
Bp294  (Blood pressure QTL 294)
Bp295  (Blood pressure QTL 295)
Bp296  (Blood pressure QTL 296)
Bp297  (Blood pressure QTL 297)
Cm61  (Cardiac mass QTL 61)
Cm62  (Cardiac mass QTL 62)
Cm63  (Cardiac mass QTL 63)
Cm64  (Cardiac mass QTL 64)
Cm65  (Cardiac mass QTL 65)
Cm66  (Cardiac mass QTL 66)
Glom10  (Glomerulus QTL 10)
Glom11  (Glomerulus QTL 11)
Glom12  (Glomerulus QTL 12)
Glom13  (Glomerulus QTL 13)
Glom14  (Glomerulus QTL 14)
Glom9  (Glomerulus QTL 9)

Strains
SR/JrHsd  (Dahl Salt-Resistant)
SS/JrHsd  (Dahl Salt-Sensitive)


Additional Information