RGD Reference Report - Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat. - Rat Genome Database

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Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.

Authors: Hodulova, M  Sedova, L  Krenova, D  Liska, F  Krupkova, M  Kazdova, L  Tremblay, J  Hamet, P  Kren, V  Seda, O 
Citation: Hodulova M, etal., PLoS One. 2014 Oct 8;9(10):e109983. doi: 10.1371/journal.pone.0109983. eCollection 2014.
RGD ID: 10402111
Pubmed: (View Article at PubMed) PMID:25296178
DOI: Full-text: DOI:10.1371/journal.pone.0109983

The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains) segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain) and two progenitor strains SHR-Lx (n = 13) and BXH2/Cub (n = 18) were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG) and cholesterol (C) concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl). We have identified 14 loci (encompassing 1 to 65 genes) on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b). Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant inbred panel of rat model strains.

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Objects Annotated

QTLs
Bw175  (Body weight QTL 175)
Kidm55  (Kidney mass QTL 55)
Livw4  (Liver weight QTL 4)
Scl69  (Serum cholesterol level QTL 69)
Scl70  (Serum cholesterol level QTL 70)
Scl71  (Serum cholesterol level QTL 71)
Scl72  (Serum cholesterol level QTL 72)
Scl73  (Serum cholesterol level QTL 73)
Scl74  (Serum cholesterol level QTL 74)
Scl75  (Serum cholesterol level QTL 75)
Scl76  (Serum cholesterol level QTL 76)
Scl77  (Serum cholesterol level QTL 77)
Scl78  (Serum cholesterol level QTL 78)
Scl79  (Serum cholesterol level QTL 79)
Scl80  (Serum cholesterol level QTL 80)
Stl33  (Serum triglyceride level QTL 33)
Stl34  (Serum triglyceride level QTL 34)

Objects referenced in this article
Strain BXH2/Cub null Rattus norvegicus
Strain PXO1/Cub null Rattus norvegicus
Strain PXO10/Cub null Rattus norvegicus
Strain PXO2/Cub null Rattus norvegicus
Strain PXO3-1/Cub null Rattus norvegicus
Strain PXO3-2/Cub null Rattus norvegicus
Strain PXO4/Cub null Rattus norvegicus
Strain PXO5-1/Cub null Rattus norvegicus
Strain PXO5-2/Cub null Rattus norvegicus
Strain PXO6-1/Cub null Rattus norvegicus
Strain PXO6-2/Cub null Rattus norvegicus
Strain PXO6-3/Cub null Rattus norvegicus
Strain PXO7-1/Cub null Rattus norvegicus
Strain PXO8-1/Cub null Rattus norvegicus
Strain PXO8-2/Cub null Rattus norvegicus
Strain PXO9/Cub null Rattus norvegicus
Strain SHR.BN-(D8Mit5-D8Mgh6)/Ipcv null Rattus norvegicus

Additional Information