Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy
Standard
Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy. / Riad, Alexander; Meyer zu Schwabedissen, Henriette; Weitmann, Kerstin; Herda, Lars R; Dörr, Marcus; Empen, Klaus; Kieback, Arne; Hummel, Astrid; Reinthaler, Marcus; Grube, Marcus; Klingel, Karin; Nauck, Matthias; Kandolf, Reinhard; Hoffmann, Wolfgang; Kroemer, Heyo K; Felix, Stephan B.
in: J BIOL CHEM, Jahrgang 287, Nr. 32, 03.08.2012, S. 27236-27243.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy
AU - Riad, Alexander
AU - Meyer zu Schwabedissen, Henriette
AU - Weitmann, Kerstin
AU - Herda, Lars R
AU - Dörr, Marcus
AU - Empen, Klaus
AU - Kieback, Arne
AU - Hummel, Astrid
AU - Reinthaler, Marcus
AU - Grube, Marcus
AU - Klingel, Karin
AU - Nauck, Matthias
AU - Kandolf, Reinhard
AU - Hoffmann, Wolfgang
AU - Kroemer, Heyo K
AU - Felix, Stephan B
PY - 2012/8/3
Y1 - 2012/8/3
N2 - 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.
AB - 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.
KW - Cardiomyopathy, Dilated/physiopathology
KW - Humans
KW - Polymorphism, Genetic
KW - Toll-Like Receptor 4/genetics
U2 - 10.1074/jbc.M112.369728
DO - 10.1074/jbc.M112.369728
M3 - SCORING: Journal article
C2 - 22645142
VL - 287
SP - 27236
EP - 27243
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 32
ER -