Polymorphisms of the Beta Adrenergic Receptor Predict Left Ventricular Remodeling Following Acute Myocardial Infarction

McLean, Rhondalyn C.; Hirsch, Glenn A.; Becker, Lewis C.; Kasch-Semenza, Laura; Gerstenblith, Gary; Schulman, Steven P.

doi:10.1007/s10557-011-6307-7

Cited by 22 publications

(16 citation statements)

References 34 publications

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“…Uninformative cancer gene modules were not included. References for part A: [79] a , [80] b , [81] c , [82] d , [83] e , [84] f , [85] g , [86] h , [87] I , [88] j , [89] k , [90] l , [91] m , [92] n , [93] o , [94] p , [95] q , [96] r , [97] s , [98] t , [99] u , [52] v , [100] w .…”

Section: Resultsmentioning

confidence: 99%

Genome-wide matching of genes to cellular roles using guilt-by-association models derived from single sample analysis

Klomp

Furge

2012

BMC Res Notes

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BackgroundHigh-throughput methods that ascribe a cellular or physiological function for each gene product are useful to understand the roles of genes that have not been extensively characterized by molecular or genetic approaches. One method to infer gene function is "guilt-by-association", in which the expression pattern of a poorly characterized gene is shown to co-vary with the expression of better-characterized genes. The function of the poorly characterized gene is inferred from the known function(s) of the well-described genes. For example, genes co-expressed with transcripts that vary during the cell cycle, development, environmental stresses, and with oncogenesis have been implicated in those processes.FindingsWhile examining the expression characteristics of several poorly characterized genes, we noted that we could associate each of the genes with a cellular phenotype by correlating individual gene expression changes with gene set enrichment scores from individual samples. We evaluated the effectiveness of this approach using a modest sized gene expression data set (expO) and a compendium of gene expression phenotypes (MSigDBv3.0). We found the transcripts that correlated best with enrichment in mitochondrial and lysosomal gene sets were mostly related to those processes (89/100 and 44/50, respectively). The reciprocal evaluation, ranking gene sets according to correlation of enrichment with an individual gene’s expression, also reflected known associations for prominent genes in the biomedical literature (16/19). In evaluating the model, we also found that 4% of the genome encodes proteins that are associated with small molecule and small peptide signal transduction gene sets, implicating a large number of genes in both internal and external environmental sensing.ConclusionsOur results show that this approach is useful to infer functions of disparate sets of genes. This method mirrors the biological experimental approaches used by others to associate individual genes with defined gene expression changes. Moreover, the approach can be used beyond discovering genes related to a cellular process to discover meaningful expression phenotypes from a compendium that are associated with a given gene. The effectiveness, versatility, and breadth of this approach make possible its application in a variety of contexts and with a variety of downstream analyses.

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Section: Resultsmentioning

confidence: 99%

Genome-wide matching of genes to cellular roles using guilt-by-association models derived from single sample analysis

Klomp

Furge

2012

BMC Res Notes

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“…Furthermore, a study of 637 patients enrolled in 2 U.S. cardiovascular genetic registries with heart failure and left ventricular dysfunction and discharged on β-blockers, angiotensin converting enzyme inhibitors or angiotensin II receptor blockers and diuretics, failed to identify a relationship between β-AR genotypes and heart failure outcomes. [5] By contrast, a study of 122 patients demonstrated that those homozygous for the β 2 -AR Glu27 genotype were over five times more likely to have maladaptive ventricular remodeling after a myocardial infarction [26] and a study of 183 patients with heart failure demonstrated that this same group would have a more robust response to β-blocker therapy. [27]…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants Are Not Associated with Outcome in Patients with Coronary Artery Disease and Left Ventricular Dysfunction: Results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) Trials

et al. 2015

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Objectives and Background: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Methods: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. Results: In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p < 0.002); however, several variants met nominal prognostic significance: variants in the β₂-adrenergic receptor gene (β₂-AR Gln27Glu) and in the A₁-adenosine receptor gene (A₁-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis. Conclusion: We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations.

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“…In Tibetan Aboriginals two genes NOS3 and ADD gene polymorphisms were associated with hypertension and the later among women particularly [113]. Similarly β1-AR polymorphism can affect LV remodeling, and both of these are more common in African Americans [114]. Among 3863 Swedish hypertensives eight novel blood pressure associated SNPs, showed no pharmacogenetic interactions for BP reduction with ββs, diltiazem or diuretics [115], while others SNPs did [116].…”

Section: Genetics In Indigenous Australiansmentioning

confidence: 99%

Contextualizing Genetics for Regional Heart Failure Care

Iyngkaran

Thomas²,

Johnson³

et al. 2016

CCR

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Congestive heart failure (CHF) is a chronic and often devastating cardiovascular disorder with no cure. There has been much advancement in the last two decades that has seen improvements in morbidity and mortality. Clinicians have also noted variations in the responses to therapies. More detailed observations also point to clusters of diseases, phenotypic groupings, unusual severity and the rates at which CHF occurs. Medical genetics is playing an increasingly important role in answering some of these observations. This developing field in many respects provides more information than is currently clinically applicable. This includes making sense of the established single gene mutations or uncommon private mutations. In this thematic series which discusses the many factors that could be relevant for CHF care, once established treatments are available in the communities; this section addresses a contextual role for medical genetics.

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Polymorphisms of the Beta Adrenergic Receptor Predict Left Ventricular Remodeling Following Acute Myocardial Infarction

Abstract: We found that polymorphisms of the β1-AR and β2-AR genes are associated with differential LV remodeling in patients treated with a β1 receptor antagonist following STEMI.

Cited by 22 publications

References 34 publications

Genome-wide matching of genes to cellular roles using guilt-by-association models derived from single sample analysis

Genome-wide matching of genes to cellular roles using guilt-by-association models derived from single sample analysis

Genetic Variants Are Not Associated with Outcome in Patients with Coronary Artery Disease and Left Ventricular Dysfunction: Results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) Trials

Contextualizing Genetics for Regional Heart Failure Care

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