Document Detail

Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy.
MedLine Citation:
PMID:  22645142     Owner:  NLM     Status:  MEDLINE    
The clinical course of patients with dilated cardiomyopathy (DCM) varies from cardiac recovery to end stage heart failure. The etiology of this variability is largely unknown. In this study, we investigated the impact of coding polymorphisms of the innate immune protein Toll-like receptor 4 (TLR4) on left ventricular performance in patients with DCM. Two variants of TLR4 (rs4986790, TLR4 c.1187A→G, p.299D→G and rs4986791,TLR4 c.1487C→T, p.T399I) were investigated in 158 patients with DCM. Other reasons for heart failure were excluded by coronary angiography, myocardial biopsy, and echocardiography. Risk factors, age, gender, or treatment did not differ among the groups. At the follow-up evaluation (median 4.0-5.4 months), patients carrying the TLR4 wild type gene displayed cardiac recovery under intense medical heart failure therapy indexed by reduced left ventricular dilation, improved left ventricular ejection fraction, and reduced NT-probrain natriuretic peptide blood level when compared with the initial evaluation. In contrast, patients carrying both the rs4986790 and the rs4986791 variant showed significantly reduced improvement of left ventricular ejection fraction (p = 0.006) and left ventricular dilation (p = 0.015) at the follow-up evaluation when compared with carriers of the wild type gene under the same treatment conditions. In addition, NT-probrain natriuretic peptide level in carriers of both TLR4 variants did not change significantly at the follow up when compared with the first evaluation. Among patients with DCM, the presence of the TLR4 variants rs4986790 and rs4986791 predicts impaired cardiac recovery independently of medical treatment or cardiac risk factors.
Alexander Riad; Henriette Meyer zu Schwabedissen; Kerstin Weitmann; Lars R Herda; Marcus Dörr; Klaus Empen; Arne Kieback; Astrid Hummel; Marcus Reinthaler; Marcus Grube; Karin Klingel; Matthias Nauck; Reinhard Kandolf; Wolfgang Hoffmann; Heyo K Kroemer; Stephan B Felix
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-29
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-06     Completed Date:  2012-11-05     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  27236-43     Citation Subset:  IM    
Department of Cardiology and Pulmonology, Universitätsmedizin Greifswald, 17475 Greifswald, Germany.
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MeSH Terms
Cardiomyopathy, Dilated / physiopathology*
Polymorphism, Genetic
Toll-Like Receptor 4 / genetics,  physiology*
Reg. No./Substance:
0/Toll-Like Receptor 4

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