RGD Reference Report - Two genomic regions of chromosomes 1 and 18 explain most of the stroke susceptibility under salt loading in stroke-prone spontaneously hypertensive rat/Izm. - Rat Genome Database

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Two genomic regions of chromosomes 1 and 18 explain most of the stroke susceptibility under salt loading in stroke-prone spontaneously hypertensive rat/Izm.

Authors: Gandolgor, TA  Ohara, H  Cui, ZH  Hirashima, T  Ogawa, T  Saar, K  Hubner, N  Watanabe, T  Isomura, M  Nabika, T 
Citation: Gandolgor TA, etal., Hypertension. 2013 Jul;62(1):55-61. doi: 10.1161/HYPERTENSIONAHA.111.00488. Epub 2013 May 20.
RGD ID: 7411685
Pubmed: PMID:23690346   (View Abstract at PubMed)
DOI: DOI:10.1161/HYPERTENSIONAHA.111.00488   (Journal Full-text)

To clarify the genetic mechanisms of stroke susceptibility in the stroke-prone spontaneously hypertensive rat (SHRSP), a quantitative trait locus (QTL) analysis was performed. Using 295 F2 rats of a cross between SHRSP/Izm and SHR/Izm, 2 major QTLs for stroke latency under salt loading were identified on chromosomes (chr) 1 and 18. Evaluation of 6 reciprocal single and double congenic rats for these QTLs showed that substitution of the SHRSP for the SHR fragment at the chr 1 and 18 QTLs increased the relative risk for stroke by 8.4 and 5.0, respectively. The combined effect of the 2 QTLs was 10x greater than that of the background genome (by Cox hazard model). Blood pressure monitoring by radio telemetry indicated that the combination of the 2 QTLs had a clear effect on the salt-dependent blood pressure increase, suggesting an important role for the salt-sensitive blood pressure increase in the susceptibility of SHRSP to stroke. A haplotype analysis of 11 substrains of SHRSP and SHR using 340 simple sequence repeat markers in the chr 1 QTL suggested that the 7-Mbp fragment between D1Rat260 and D1Rat178 was most likely to harbor the responsible gene(s), which was confirmed by a study of additional subcongenic strains. This study indicated a major role for 2 QTLs on chr 1 and 18 in stroke susceptibility in SHRSP under salt loading. The salt-sensitive blood pressure increase was implied to play a key role in the stroke susceptibility.



Disease Annotations    
hypertension  (IAGP)
Hypotension  (IAGP)
Stroke  (IAGP)

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

QTLs
Strs4  (Sensitivity to stroke QTL 4)
Strs5  (Sensitivity to stroke QTL 5)
Strs6  (Sensitivity to stroke QTL 6)
Strs7  (Sensitivity to stroke QTL 7)

Objects referenced in this article
Strain SHR.SHRSP-(D18Rat73-D18Rat11)/Izm null Rattus norvegicus
Strain SHR.SHRSP-(D1Rat93-D1Rat269)/Izm null Rattus norvegicus
Strain SHRSP.SHR-(D1Rat93-D1Rat269)(D18Rat73-D18Rat11)/Izm null Rattus norvegicus
QTL Strs1 Sensitivity to stroke QTL 1 Rattus norvegicus

Additional Information