RRC ID |
27717
|
著者 |
Gandolgor TA, Ohara H, Cui ZH, Hirashima T, Ogawa T, Saar K, Hübner N, Watanabe T, Isomura M, Nabika T.
|
タイトル |
Two genomic regions of chromosomes 1 and 18 explain most of the stroke susceptibility under salt loading in stroke-prone spontaneously hypertensive rat/Izm.
|
ジャーナル |
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.
|
巻・号 |
62(1)
|
ページ |
55-61
|
公開日 |
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
|
引用数 |
13
|
WOS 分野
|
PERIPHERAL VASCULAR DISEASE
|
リソース情報 |
ラット |
SHR/NCrlCrlj(strainID=478) |