COSEGREGATION OF THE <i>Tnfα</i> LOCUS WITH CARDIOVASCULAR PHENOTYPES IN THE F<sub>2</sub> GENERATION OF A NEW ZEALAND GENETICALLY HYPERTENSIVE AND BROWN NORWAY CROSS

Harris, Eugenie L.; Grigor, Murray R.; Thompson, Caryn M.

doi:10.1111/j.1440-1681.1998.t01-17-.x

Cited by 4 publications

(3 citation statements)

References 20 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29 A BP QTL within the same region of rat chromosome 20 was also identified in a cross involving New Zealand genetically hypertensive and BN rats. 45 No significant effect of the differential segment was found in some other studies, however. 28,46 …”

Section: Discussionmentioning

confidence: 64%

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

et al. 2003

View full text Add to dashboard Cite

Abstract-Previous linkage and association studies have suggested that a region of human chromosome 6 containing the tumor necrosis factor (TNF)-␣ gene is involved in the pathogenesis of obesity and obesity-associated hypertension. The aim of the present investigation was to establish whether a segment of rat chromosome 20 (RNO20), which also contains the TNF-␣ gene, determines diet-induced changes in adiposity and blood pressure (BP). The results showed that a transfer of the RNO20 segment from the normotensive Brown Norway (BN) rat onto the background of the spontaneously hypertensive rat (SHR) is associated with a significantly greater increase in adiposity, glucose intolerance, circulating leptin levels, and BP during 12-week, high-fat-diet feeding. In contrast, the transfer is not associated with significant changes in these variables during 12-week, normal-diet feeding. In addition, sequencing of the TNF-␣ gene revealed differences between SHR and BN in the 5Ј-and 3Ј-regulatory regions of the gene. Subsequent analyses of TNF-␣ gene expression in fat, muscle, and liver, however, did not provide support for the functional involvement of these differences. In summary, the investigated RNO20 segment contains 1 or more gene variants that affect adiposity, glucose tolerance, serum leptin levels, and BP, but only when the animals are exposed to a particular environment, ie, high-fat-diet feeding. Further studies are needed to identify genes mediating these effects. Considering current changes in our lifestyle involving an increased calorie and fat intake, we believe that gene-environment interactions, such as those described here, play an important role in the current epidemic of obesity and obesityassociated hypertension.

show abstract

Section: Discussionmentioning

confidence: 64%

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

et al. 2003

View full text Add to dashboard Cite

show abstract

“…While associations between some cardiovascular phenotypes and several candidate gene alleles (GCA, REN, TNF α) in GH rats have already been reported in a GH × BN intercross (19,40,41), we report, for the first time, all data and results of the complete genome scan including QTL for five of the six measured or derived traits on six different chromosomes. Three major blood pressure QTL in the GH rat were identified (1 significant QTL on chromosome 6 and 2 suggestive on chromosomes 2 and 18).…”

Section: Discussionmentioning

confidence: 99%

Genetically Hypertensive Brown Norway Congenic Rat Strains Suggest Intermediate Traits Underlying Genetic Hypertension

et al. 2008

View full text Add to dashboard Cite

Aim To determine the independent and combined effects of three quantitative trait loci (QTL) for blood pressure in the Genetically Hypertensive (GH/Omr) rat by generating and characterizing single and combined congenic strains that have QTL on rat chromosomes (RNO) 2, 6, and 18 from the GH rat introduced into a hypertension resistant Brown Norway (BN) background.Methods Linkage analysis and QTL identification (genome wide QTL scan) were performed with MapMaker/EXP to build the genetic maps and MapMaker/QTL for linking the phenotypes to the genetic map. The congenic strains were derived using marker-assisted selection strategy from a single male F1 offspring of an intercross between the male GH/Omr and female BN/Elh, followed by 10 generations of selective backcrossing to the female BN progenitor strain. Single congenic strains generated were BN.GH-(D2Rat22-D2Mgh11)/Mcwi (BN.GH2); BN.GH-(D6Mit12-D6Rat15)/Mcwi (BN.GH6); and BN.GH-(D18Rat41-D18Mgh4)/Mcwi (BN.GH18). Blood pressure measurements were obtained either via a catheter placed in the femoral artery or by radiotelemetry in the single and combined congenics. Responses to angiotensin II (ANGII), norepinephrine (NE), and baroreceptor sensitivity were measured in the single congenics.Results Transferring one or more QTL from the hypertensive GH into normotensive BN strain was not sufficient to cause hypertension in any of the developed congenic strains. There were no differences between the parental and congenic strains in their response to NE. However, BN.GH18 rats revealed significantly lower baroreceptor sensitivity (β = -1.25 ± 0.17), whereas BN.GH2 (β = 0.66 ± 0.09) and BN.GH18 (β = 0.71 ± 0.07) had significantly decreased responses to ANGII from those observed in the BN (β = 0.88 ± 0.08). ConclusionThe failure to alter blood pressure levels by introducing the hypertensive QTL from the GH into the hypertension resistant BN background suggests that the QTL effects are genome backgrounddependent in the GH rat. BN.GH2 and BN.GH18 rats reveal significant differences in response to ANGII and impaired baroreflex sensitivity, suggesting that we may have captured a locus responsible for the genetic control of baroreceptor sensitivity, which would be considered an intermediate phenotype of blood pressure.

show abstract

“…20 In addition, the body temperature response to lipopolysaccharide differs between SHR and its normotensive control, 33 and it has been demonstrated that this response is, at least in part, determined by the TNF-␣ gene locus. 34 Finally, the TNF-␣ gene locus as a part of the RT1 complex has been suggested in some, 35,36 but not all, 37,38 studies to contribute to the pathogenesis of hypertension in SHR and New Zealand genetically hypertensive rats. In the present study, the effect of the TNF-␣ gene locus on both obesity and obesity-associated hypertension was found to be most significant in nonmorbidly obese individuals.…”

Section: Discussionmentioning

confidence: 99%

Role of Tumor Necrosis Factor-α Gene Locus in Obesity and Obesity-Associated Hypertension in French Canadians

et al. 2000

View full text Add to dashboard Cite

Abstract-Obesity represents a serious risk factor for the development of cardiovascular diseases, including hypertension.Segregation studies suggest that obesity and obesity-associated hypertension may share some genetic determinants. The results of the present candidate gene investigation suggest that in hypertensive pedigrees of French-Canadian origin, one such determinant is the tumor necrosis factor (TNF)-␣ gene locus. Gender-pooled quantitative sib-pair analysis demonstrated a significant effect of the gene locus on 3 global and 7 regional measures of obesity (Pϭ0.05 to 0.0004).Gender-separate quantitative sib-pair analyses showed that the impact of the locus on obesity is most significant in the abdominal region in men and in the thigh region in women. Furthermore, the haplotype relative-risk test demonstrated a significant association between the TNF-␣ gene locus and both obesity (Pϭ0.006) and obesity-associated hypertension (Pϭ0.02). These effects were most significant in individuals with nonmorbid obesity. In conclusion, the results of linkage and association analyses suggest that in hypertensive pedigrees of French-Canadian origin, the TNF-␣ gene locus contributes to the determination of obesity and obesity-associated hypertension. In addition, the data indicate that gender modifies the effect of the locus on the regional distribution of body fat. (Hypertension. 2000;36:14-19.)

show abstract

COSEGREGATION OF THE Tnfα LOCUS WITH CARDIOVASCULAR PHENOTYPES IN THE F₂ GENERATION OF A NEW ZEALAND GENETICALLY HYPERTENSIVE AND BROWN NORWAY CROSS

Cited by 4 publications

References 20 publications

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

Genetically Hypertensive Brown Norway Congenic Rat Strains Suggest Intermediate Traits Underlying Genetic Hypertension

Role of Tumor Necrosis Factor-α Gene Locus in Obesity and Obesity-Associated Hypertension in French Canadians

Contact Info

Product

Resources

About

COSEGREGATION OF THE Tnfα LOCUS WITH CARDIOVASCULAR PHENOTYPES IN THE F2 GENERATION OF A NEW ZEALAND GENETICALLY HYPERTENSIVE AND BROWN NORWAY CROSS

Cited by 4 publications

References 20 publications

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

Genetically Hypertensive Brown Norway Congenic Rat Strains Suggest Intermediate Traits Underlying Genetic Hypertension

Role of Tumor Necrosis Factor-α Gene Locus in Obesity and Obesity-Associated Hypertension in French Canadians

Contact Info

Product

Resources

About

COSEGREGATION OF THE Tnfα LOCUS WITH CARDIOVASCULAR PHENOTYPES IN THE F₂ GENERATION OF A NEW ZEALAND GENETICALLY HYPERTENSIVE AND BROWN NORWAY CROSS