論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ラット | SHR/NCrlCrlj(strainID=478) |