Quantitative trait loci influencing cholesterol and phospholipid phenotypes map to chromosomes that contain genes regulating blood pressure in the spontaneously hypertensive rat.

Abstract

The frequent coincidence of hypertension and dyslipidemia suggests that related genetic factors might underlie these common risk factors for cardiovascular disease. To investigate whether quantitative trait loci (QTLs) regulating lipid levels map to chromosomes known to contain genes regulating blood pressure, we used a genome scanning approach to map QTLs influencing cholesterol and phospholipid phenotypes in a large set of recombinant inbred strains and in congenic strains derived from the spontaneously hypertensive rat and normotensive Brown-Norway (BN.Lx) rat fed normal and high cholesterol diets. QTLs regulating lipid phenotypes were mapped by scanning the genome with 534 genetic markers. A significant relationship ( P Ͻ 0.00006) was found between basal HDL2 cholesterol levels and the

Enhanced insulin secretion and cholesterol metabolism in congenic strains of the spontaneously diabetic (Type 2) Goto Kakizaki rat are controlled by independent genetic loci in rat chromosome 8

“…The locus Obs3, which is linked to obesity phenotypes in a cross derived from the Otsuka Long-Evans Tokushima fatty (OLETF) rat model for Type 2 diabetes and obesity and F344 controls, coincides almost exactly with the region of Nidd/gk5 linked to body weight [17]. Other QTL for fasting plasma TG in the OLETF rat [18] and plasma HDL2 cholesterol and PL levels in a recombinant inbred panel derived from the spontaneously hypertensive rat (SHR) and the BN rat [19] have also been reported in this region of rat chromosome 8. These observations led us to extend the phenotype screening of our congenics beyond the variables characterising Nidd/gk5 in the GKxBN F2 cross.…”

“…This hypothesis is supported by the fact that glucose intolerance was the sole criterion used in the production of the GK strain through selective breedings [3]. The fact that Chol/gk1 coincides with a locus linked to cholesterol metabolism in a BN-SHR strain combination [19] and that high blood pressure was the sole parameter used to derive the SHR strain, may also indicate an effect of gene(s) underlying strain differences. In addition, at the rat obesity locus Obs3, alleles originating from the control F344 strain contribute to increased fat pad weight, which may therefore be unrelated to obesity in the OLETF rat [17].…”

Genetic control of plasma lipid levels in a cross derived from normoglycaemic Brown Norway and spontaneously diabetic Goto–Kakizaki rats

“…In rats the genetic control of plasma lipid variables has been addressed in the context of hypertension [23][24][25], stroke [25], obesity [26] and hypertriglyceridaemia [27] using experimental crosses and mapping panels derived from genetically different inbred control and disease strains. Here we identify a new locus Pl/gk1 that co-localises with a QTL linked to the level of plasma triglycerides and cholesterol in a cross derived from the spontaneously obese Otsuka Long-Evans Tokushima Fatty (OLETF) strain [27].…”

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

“…Most of these studies examined the impact of a high-fat/high-cholesterol diet on serum lipids. 29,39,40 To the best of our knowledge, however, the effect of HFD on adiposity and BP has not been compared between SHR and BN. It has been demonstrated, though, that SHR compared with other normotensive strains, namely, Wistar-Kyoto or Sprague-Dawley rats, are resistant to weight gain in response to HFD feeding; they either do not increase BW 41 or increase it less than does the normotensive strain.…”