RRC ID 27717
Author Gandolgor TA, Ohara H, Cui ZH, Hirashima T, Ogawa T, Saar K, Hübner N, Watanabe T, Isomura M, Nabika T.
Title Two genomic regions of chromosomes 1 and 18 explain most of the stroke susceptibility under salt loading in stroke-prone spontaneously hypertensive rat/Izm.
Journal Hypertension
Abstract 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 10× 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.
Volume 62(1)
Pages 55-61
Published 2013-7-1
DOI 10.1161/HYPERTENSIONAHA.111.00488
PII HYPERTENSIONAHA.111.00488
PMID 23690346
MeSH Animals Animals, Congenic Blood Pressure / drug effects Blood Pressure / genetics Chromosomes, Mammalian / genetics* DNA / genetics* Disease Models, Animal Genetic Predisposition to Disease* Genotype Hypertension / complications Hypertension / genetics* Hypertension / physiopathology Male Microsatellite Repeats Quantitative Trait Loci Rats Rats, Inbred SHR Sodium Chloride, Dietary / toxicity Stroke / etiology Stroke / genetics* Stroke / physiopathology
IF 7.713
Times Cited 13
WOS Category PERIPHERAL VASCULAR DISEASE
Resource
Rats SHR/NCrlCrlj(strainID=478)