Browsing by Subject "Cardiac hypertrophy"

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    Open Access
    Common variation neighbouring micro-RNA 22 is associated with increased left ventricular mass
    (Public Library of Science, 2013) Harper, Andrew R; Mayosi, Bongani M; Rodriguez, Antony; Rahman, Thahira; Hall, Darroch; Mamasoula, Chrysovalanto; Avery, Peter J; Keavney, Bernard D
    AIMS: Previous genome-wide linkage analysis has suggested that chromosomal region 17p13.3 may harbour genes influencing left ventricular mass (LVM) in man. To date, the genetic factors accounting for LVM variability remain largely unknown but a non-coding RNA gene within this region, micro-RNA 22 (miR-22) , has been implicated in cardiac hypertrophy and heart failure in animal models. We thus investigated the relationship between common genetic polymorphisms surrounding miR-22 and left ventricular mass in a family-based association study. Methods and RESULTS: We studied a cohort of 255 families comprising 1,425 individuals ascertained via a hypertensive proband. Ten single nucleotide polymorphisms which together tagged common genetic variation surrounding the miR-22 gene were genotyped. There was evidence of association between the rs7223247 polymorphism, which lies within the 3′UTR of a gene of unknown function, TLCD2, immediately downstream from miR-22, and left ventricular mass determined by Sokolow-Lyon voltage (Bonferroni corrected p- value = 0.038). The T allele at rs7223247 was associated with an 0.272 standard deviation higher Sokolow-Lyon voltage. Genotype was responsible for ∼1% of the population variability in LVM. CONCLUSIONS: Genotype at the rs7223247 polymorphism affects left ventricular mass determined by Sokolow-Lyon voltage. The neighbouring genes miR-22 and TLCD2 are strong candidates to account for this observation.
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    Open Access
    RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response
    (2016) Bergmann, Sven
    Abstract Background The transcriptional response to many widely used drugs and its modulation by genetic variability is poorly understood. Here we present an analysis of RNAseq profiles from heart tissue of 18 inbred mouse strains treated with the β-blocker atenolol (ATE) and the β-agonist isoproterenol (ISO). Results Differential expression analyses revealed a large set of genes responding to ISO (n = 1770 at FDR = 0.0001) and a comparatively small one responding to ATE (n = 23 at FDR = 0.0001). At a less stringent definition of differential expression, the transcriptional responses to these two antagonistic drugs are reciprocal for many genes, with an overall anti-correlation of r = −0.3. This trend is also observed at the level of most individual strains even though the power to detect differential expression is significantly reduced. The inversely expressed gene sets are enriched with genes annotated for heart-related functions. Modular analysis revealed gene sets that exhibit coherent transcription profiles across some strains and/or treatments. Correlations between these modules and a broad spectrum of cardiovascular traits are stronger than expected by chance. This provides evidence for the overall importance of transcriptional regulation for these organismal responses and explicits links between co-expressed genes and the traits they are associated with. Gene set enrichment analysis of differentially expressed groups of genes pointed to pathways related to heart development and functionality. Conclusions Our study provides new insights into the transcriptional response of the heart to perturbations of the β-adrenergic system, implicating several new genes that had not been associated to this system previously.