Effects of chromosome 17 on features of the metabolic syndrome in the Lyon hypertensive rat

Gilibert, Sophie; Kwitek, Anne E.; Hübner, Norbert; Tschannen, Michael; Jacob, Howard J.; Sassard, J; Bataillard, Alain

doi:10.1152/physiolgenomics.00262.2007

Cited by 17 publications

(21 citation statements)

References 29 publications

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“…Figure 1 shows, as previously described [25], that LH rats exhibit a much larger body weight than BN rats. Interestingly, LH-13 BN rats showed a significantly larger body weight than LH rats, while body weight was lower in BN-13 LH rats than in BN parents.…”

Section: Resultssupporting

confidence: 77%

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Implication of chromosome 13 on hypertension and associated disorders in Lyon hypertensive rats

Gilibert

Bataillard

Nussberger³

et al. 2009

Journal of Hypertension

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Hypertension and associated disorders are major risk factors for cardiovascular disease. The Lyon Hypertensive rat (LH) is a genetically hypertensive strain that exhibits spontaneous and saltsensitive hypertension, exaggerated proteinuria, high body weight, hyperlipidemia and elevated insulin-to-glucose ratio. Previous genetic mapping identified Quantitative Trait Loci (QTL) influencing blood pressure on chromosome 13 (RNO13) in several models of hypertension. To study the effects of a single chromosome on the mapped traits, we generated consomic strains by substituting LH RNO13 with that of the normotensive Brown Norway (BN) strain (LH-13 BN ) and reciprocal consomics by substituting a BN RNO13 with that of LH (BN-13 LH ). These reciprocal consomic strains, as well as the two parental strains were characterized for blood pressure, metabolic and morphological parameters. Compared to LH parents, LH-13 BN rats showed decreased mean blood pressure (up to −24 mmHg on 2%NaCl in the drinking water), urine proteins and lipids, and increased body weight. Differences between BN-13 LH and BN rats are much smaller than those observed between LH-13 BN and LH rats, demonstrating the effects of the highly resistant BN genome background. Plasma renin activity is not affected by the substitution of RNO13, despite the significant blood pressure differences.The present work demonstrates that RNO13 is a determinant of BP, proteinuria, and plasma lipids in the LH rat. The distinct phenotypic differences between the consomic LH-13 BN and the LH make it a powerful model to determine genes and pathways leading to these risk factors for cardiovascular and renal disease.

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Section: Resultssupporting

confidence: 77%

“…Consequently, the parental strains were the same as in our previous study [25] and the framework of the protocol is identical for all the strains, as previously described, with the exception that some biochemical measurements differ among the different consomic strains, as described below.…”

Section: Methodsmentioning

confidence: 99%

Implication of chromosome 13 on hypertension and associated disorders in Lyon hypertensive rats

Gilibert

Bataillard

Nussberger³

et al. 2009

Journal of Hypertension

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“…[112][113][114] Results of this approach make it clear that the SS phenotype of rats is determined by multiple different genes or by the combination of their effects into a polygenic form of inheritance. An additional contribution of this methodology has been the understanding that components of the SS phenotype (eg, insulin resistance 115 ) or the magnitude of its cardiac 98,116 and renal 99,[117][118][119] target organ damage may be determined by genetic influences distinct from those that control the hypertensive response to salt.…”

Section: Genetics and Ss Phenotype In Rodentsmentioning

confidence: 99%

Salt Sensitivity of Blood Pressure

Elijovich¹,

Weinberger²,

Anderson³

et al. 2016

Hypertension

386

230

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The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 23, 2016, and the American Heart Association Executive Committee on February 23, 2016. A copy of the document is available at http://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com.The American Heart Association requests that this document be cited as follows: Elijovich F, Weinberger MH, Anderson CAM, Appel LJ, Bursztyn M, Cook NR, Dart RA, Newton-Cheh CH, Sacks FM, Laffer CL; on behalf of the American Heart Association Professional and Public Education Committee of the Council on Hypertension; Council on Functional Genomics and Translational Biology; and Stroke Council. Salt sensitivity of blood pressure: a scientific statement from the American Heart Association. Hypertension. 2016;68:e7-e46. doi: 10.1161/HYP.0000000000000047.Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit http://professional.heart.org/statements. Select the "Guidelines & Statements" drop-down menu, then click "Publication Development."Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/CopyrightPermission-Guidelines_UCM_300404_Article.jsp. A link to the "Copyright Permissions Request Form" appears on the right side of the page. Figure 2 shows the major effect of aging in increasing the prevalence of SSBP in both normotensive and hypertensive subjects. An important and encouraging observation is that the multiple phenotypic characteristics described in pure SS strains of rodents reproduce those observed in humans, indicating that the phenotypic cluster of SSBP can be brought out in humans by the current techniques used in carefully controlled research. Additionally, despite the unquestionable influence of environmental factors in the determination of SSBP in humans, estimates of its heritability have been as high as 74% in blacks 9 and 50% in Chinese subjects, 10 both higher than those for hypertension. Salt Sensitivity of Blood PressureAn important issue is the clinical significance of the SSBP phenotype. There was increasing understanding that it represents an abnormality. The reasons w...

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“…8, 34 Therefore, we speculate there may be a gene or genes having pleiotropic effects on the MetS spectrum. In this study, we identified a cis -regulated gene on RNO17, RGD1562963 , as a putative driver gene regulating multiple downstream genes.…”

Section: Discussionmentioning

confidence: 96%

Systems Biology With High-Throughput Sequencing Reveals Genetic Mechanisms Underlying the Metabolic Syndrome in the Lyon Hypertensive Rat

Wang

John

Mennie

et al. 2015

Circ Cardiovasc Genet

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Background The metabolic syndrome (MetS) is a collection of co-occurring complex disorders including obesity, hypertension, dyslipidemia, and insulin resistance. The Lyon Hypertensive (LH) and Lyon Normotensive (LN) rats are models of MetS sensitivity and resistance, respectively. To identify genetic determinants and mechanisms underlying MetS, an F2 intercross between LH and LN was comprehensively studied. Methods and Results Multi-dimensional data were obtained including genotypes of 1536 SNPs, 23 physiological traits and more than 150 billion nucleotides of RNA-seq reads from the livers of F2 intercross offspring and parental rats. Phenotypic and expression QTL were mapped. Application of systems biology methods identified 17 candidate MetS genes. Several putative causal cis-eQTL were identified corresponding with pQTL loci. We found an eQTL hotspot on rat chromosome 17 that is causally associated with multiple MetS-related traits, and found RGD1562963, a gene regulated in cis by this eQTL hotspot, as the most likely eQTL driver gene directly affected by genetic variation between LH and LN rats. Conclusions Our study sheds light on the intricate pathogenesis of MetS and demonstrates that systems biology with high-throughput sequencing is a powerful method to study the etiology of complex genetic diseases.

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Effects of chromosome 17 on features of the metabolic syndrome in the Lyon hypertensive rat

Cited by 17 publications

References 29 publications

Implication of chromosome 13 on hypertension and associated disorders in Lyon hypertensive rats

Implication of chromosome 13 on hypertension and associated disorders in Lyon hypertensive rats

Salt Sensitivity of Blood Pressure

Systems Biology With High-Throughput Sequencing Reveals Genetic Mechanisms Underlying the Metabolic Syndrome in the Lyon Hypertensive Rat

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