| pubmed-article:18425130 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18425130 | lifeskim:mentions | umls-concept:C0018801 | lld:lifeskim |
| pubmed-article:18425130 | lifeskim:mentions | umls-concept:C0034785 | lld:lifeskim |
| pubmed-article:18425130 | lifeskim:mentions | umls-concept:C1514762 | lld:lifeskim |
| pubmed-article:18425130 | lifeskim:mentions | umls-concept:C1333699 | lld:lifeskim |
| pubmed-article:18425130 | lifeskim:mentions | umls-concept:C1882417 | lld:lifeskim |
| pubmed-article:18425130 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:18425130 | pubmed:dateCreated | 2008-5-8 | lld:pubmed |
| pubmed-article:18425130 | pubmed:abstractText | Beta-adrenergic receptor (betaAR) blockade is a standard therapy for cardiac failure and ischemia. G protein-coupled receptor kinases (GRKs) desensitize betaARs, suggesting that genetic GRK variants might modify outcomes in these syndromes. Re-sequencing of GRK2 and GRK5 revealed a nonsynonymous polymorphism of GRK5, common in African Americans, in which leucine is substituted for glutamine at position 41. GRK5-Leu41 uncoupled isoproterenol-stimulated responses more effectively than did GRK5-Gln41 in transfected cells and transgenic mice, and, like pharmacological betaAR blockade, GRK5-Leu41 protected against experimental catecholamine-induced cardiomyopathy. Human association studies showed a pharmacogenomic interaction between GRK5-Leu41 and beta-blocker treatment, in which the presence of the GRK5-Leu41 polymorphism was associated with decreased mortality in African Americans with heart failure or cardiac ischemia. In 375 prospectively followed African-American subjects with heart failure, GRK5-Leu41 protected against death or cardiac transplantation. Enhanced betaAR desensitization of excessive catecholamine signaling by GRK5-Leu41 provides a 'genetic beta-blockade' that improves survival in African Americans with heart failure, suggesting a reason for conflicting results of beta-blocker clinical trials in this population. | lld:pubmed |
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| pubmed-article:18425130 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18425130 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18425130 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:18425130 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18425130 | pubmed:month | May | lld:pubmed |
| pubmed-article:18425130 | pubmed:issn | 1546-170X | lld:pubmed |
| pubmed-article:18425130 | pubmed:author | pubmed-author:LiggettStephe... | lld:pubmed |
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| pubmed-article:18425130 | pubmed:author | pubmed-author:KochWalter... | lld:pubmed |
| pubmed-article:18425130 | pubmed:author | pubmed-author:DornGerald... | lld:pubmed |
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| pubmed-article:18425130 | pubmed:author | pubmed-author:SparksLiL | lld:pubmed |
| pubmed-article:18425130 | pubmed:author | pubmed-author:HahnHarvey... | lld:pubmed |
| pubmed-article:18425130 | pubmed:author | pubmed-author:DiwanAbhinavA | lld:pubmed |
| pubmed-article:18425130 | pubmed:author | pubmed-author:SyedFaisal... | lld:pubmed |
| pubmed-article:18425130 | pubmed:author | pubmed-author:CresciSharonS | lld:pubmed |
| pubmed-article:18425130 | pubmed:author | pubmed-author:ParekhRohan... | lld:pubmed |
| pubmed-article:18425130 | pubmed:author | pubmed-author:KellyReagan... | lld:pubmed |
| pubmed-article:18425130 | pubmed:author | pubmed-author:MartiniJeffre... | lld:pubmed |
| pubmed-article:18425130 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18425130 | pubmed:volume | 14 | lld:pubmed |
| pubmed-article:18425130 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18425130 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18425130 | pubmed:pagination | 510-7 | lld:pubmed |
| pubmed-article:18425130 | pubmed:dateRevised | 2011-4-15 | lld:pubmed |
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