Identification of Quantitative Trait Loci for Cardiac Hypertrophy in Two Different Strains of the Spontaneously Hypertensive Rat

Inomata, Hyoe; Watanabe, Takeshi; Ikoma, Yoko; Liang, Yi-Qiang; Mashimo, Tomoji; Nabika, Toru; Ikeda, Katsumi; Yanai, Kazuyuki; Gotoda, Takanari; Yamori, Yukio; Isobe, Mitsuaki; Kato, Norihiro

doi:10.1291/hypres.28.273

Cited by 15 publications

(16 citation statements)

References 35 publications

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“…[37][38][39][40] In the present study we observed significant equivalent reductions in CMI and LVMI in SP.WKY Gla 2a and SP.WKY Gla 3a strains compared with the SHRSP. However, these changes in heart mass occurred in parallel with the observed BP reductions during baseline and salt-loading periods.…”

Section: Discussionsupporting

confidence: 67%

Interaction Between Chromosome 2 and 3 Regulates Pulse Pressure in the Stroke-Prone Spontaneously Hypertensive Rat

Koh-Tan

McBride²,

McClure³

et al. 2013

Hypertension

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H uman essential hypertension is a complex, multifactorial, quantitative trait under polygenic control, with inherited factors contributing ≤30% of the variation in blood pressure (BP). 1 The search for the specific genetic variations contributing to this heritability remains challenging. Recent genome-wide association studies collectively explain only a very small proportion of the total variation in systolic BP (SBP) or diastolic BP (DBP; ≈2.2%), 2,3 which suggests the existence of many more undiscovered BP-related variants.Genetic detection of complex polygenic diseases is complicated by potential gene-gene, gene-environment interactions, and nonsequence epigenetic modifications. In particular, there is growing evidence for epistasis among BP quantitative trait loci (QTL) in inbred rat models of hypertension. 4-11We have previously identified BP QTL on rat chromosomes (RNO) 2 and RNO3 in a linkage analysis of an F2 cross between stroke-prone spontaneously hypertensive (SHRSP) and Wistar Kyoto (WKY) rats. 12 We subsequently confirmed the RNO2 loci with the production of congenic strains and identified candidate genes for baseline BP and response to salt loading. [13][14][15] The aims of this study were to confirm the RNO3 QTL and to investigate interaction between the loci on RNO2 and RNO3 through the generation and phenotypic assessment of single and bicongenic strains. Methods Animal StrainsInbred colonies of SHRSP and WKY have been developed and maintained at the University of Glasgow since 1991, as described previously.12 All animals were housed under controlled environmental conditions, fed standard rat chow (rat and mouse no No. 1 maintenance diet, Special Diet Services) and water provided ad libitum. At 18 weeks of age, rats were given a salt challenge (1% NaCl in drinking water) for 3 weeks. All animal procedures performed were approved Abstract-In an F2 cross between stroke-prone spontaneously hypertensive (SHRSP) and Wistar Kyoto (WKY) rats, we previously identified blood pressure quantitative trait loci (QTL) on rat chromosome (RNO) 2 and a pulse pressure QTL on RNO3. The aims of this study were to confirm the QTL on RNO3 and to investigate interaction between RNO2 and RNO3 loci through the generation and phenotypic assessment of single RNO3 congenic (SP.WKY Gla 3a) and bicongenic (SP.WKY Gla 2a/3a) strains. Hemodynamic profiling, vascular function, and renal histology were examined in these newly generated strains along with the previously reported RNO2 congenic strain (SP.WKY Gla 2a). Our results demonstrate significant equivalent reduction in systolic, diastolic, and pulse pressure phenotypes in SP.WKY Gla 3a and SP.WKY Gla 2a rats, whereas greater reductions were observed with the SP.WKY Gla 2a/3a bicongenic strain achieving blood pressure levels similar to normotensive WKY rats. Epistasis was observed between pulse pressure QTL on RNO2 and 3 at baseline and during 1% salt challenge. Vascular function and renal pathology studies indicate that QTL on RNO3 are responsible for salt-induced kidney p...

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Section: Discussionsupporting

confidence: 67%

Interaction Between Chromosome 2 and 3 Regulates Pulse Pressure in the Stroke-Prone Spontaneously Hypertensive Rat

Koh-Tan

McBride²,

McClure³

et al. 2013

Hypertension

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“…Similar situations have been observed in the genetic analyses of spontaneously hypertensive rats, another prevalently used genetic model for hypertension (19). The concept of a gene is now being re-evaluated (20).…”

Section: Fig 7 Effect Of Comt Inhibitor On Blood Pressure (Bp) Levesupporting

confidence: 53%

Exclusion of the Catechol-O-Methyltransferase Gene from Genes Contributing to Salt-Sensitive Hypertension in Dahl Salt-Sensitive Rats

et al. 2007

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“…The experimental data reported thus far suggests that ACE plays a role in the pathogenesis of LVH. Moreover, several studies have investigated the influence of genetic background on the variability in left ventricular mass in humans, and the heritability of this trait has been estimated to be between 30% and 70% in different populations (29). Saeed et al (30) first showed that the ACE 2350 G/A polymorphism is associated with increased risk of LVH in a nonhypertensive Emirati population.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-Converting Enzyme Gene 2350 G/A Polymorphism Is Associated with Left Ventricular Hypertrophy but Not Essential Hypertension

et al. 2007

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Identification of Quantitative Trait Loci for Cardiac Hypertrophy in Two Different Strains of the Spontaneously Hypertensive Rat

Cited by 15 publications

References 35 publications

Interaction Between Chromosome 2 and 3 Regulates Pulse Pressure in the Stroke-Prone Spontaneously Hypertensive Rat

Interaction Between Chromosome 2 and 3 Regulates Pulse Pressure in the Stroke-Prone Spontaneously Hypertensive Rat

Exclusion of the Catechol-O-Methyltransferase Gene from Genes Contributing to Salt-Sensitive Hypertension in Dahl Salt-Sensitive Rats

Angiotensin-Converting Enzyme Gene 2350 G/A Polymorphism Is Associated with Left Ventricular Hypertrophy but Not Essential Hypertension

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