Meta-Analysis of Genome-Wide Gene Expression Differences in Onset and Maintenance Phases of Genetic Hypertension
pmid: 20585107
Meta-Analysis of Genome-Wide Gene Expression Differences in Onset and Maintenance Phases of Genetic Hypertension
Gene expression differences accompany both the onset and established phases of hypertension. By an integrated genome-transcriptome approach we performed a meta-analysis of data from 74 microarray experiments available on public databases to identify genes with altered expression in the kidney, adrenal, heart, and artery of spontaneously hypertensive and Lyon hypertensive rats. To identify genes responsible for the onset of hypertension we used a statistical approach that sought to eliminate expression differences that occur during maturation unrelated to hypertension. Based on this adjusted fold-difference statistic, we found 36 genes for which the expression differed between the prehypertensive phase and established hypertension. Genes having possible relevance to hypertension onset included Actn2, Ankrd1, ApoE, Cd36, Csrp3, Me1, Myl3, Nppa, Nppb, Pln, Postn, Spp1 , Slc21a4, Slc22a2, Thbs4 , and Tnni3. In established hypertension 102 genes exhibited altered expression after Bonferroni correction ( P <0.05). These included Atp5o, Ech1, Fabp3, Gnb3, Ldhb, Myh6, Lpl, Pkkaca, Vegfb, Vcam1 , and reduced nicotinamide-adenine dinucleotide dehydrogenases. Among the genes identified, there was an overrepresentation of gene ontology terms involved in energy production, fatty acid and lipid metabolism, oxidation, and transport. These could contribute to increases in reactive oxygen species. Our meta-analysis has revealed many new genes for which the expression is altered in hypertension, so pointing to novel potential causative, maintenance, and responsive mechanisms and pathways.
- University of Sydney Australia
Models, Genetic, Fatty Acids, Lipids, Oxidative Phosphorylation, Rats, Gene Expression Regulation, Rats, Inbred SHR, Hypertension, Animals, Age of Onset, Energy Metabolism, Genome-Wide Association Study, Oligonucleotide Array Sequence Analysis
Models, Genetic, Fatty Acids, Lipids, Oxidative Phosphorylation, Rats, Gene Expression Regulation, Rats, Inbred SHR, Hypertension, Animals, Age of Onset, Energy Metabolism, Genome-Wide Association Study, Oligonucleotide Array Sequence Analysis
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