ABSTRACT
OBJECTIVE@#Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation.@*METHODS@#We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotype-phenotype correlation analysis.@*RESULTS@#The A allele of rs4468255 was significantly associated with IDCM (P<0.01). The rs4468255, rs11812601, rs56165849, and rs3740346 were also associated with diastolic blood pressure (DBP) and left ventricular ejection fraction (LVEF) (P<0.05). Notably, a higher frequency of rs4468255 polymorphism was observed in implantable cardioverter defibrillator (ICD) recipients under a recessive model (P<0.01), whereas the significant association disappeared after adjusting for potential confounders. However, in the dominant model, notable correlations could only be observed after adjusting for multi parameters.@*CONCLUSIONS@#The rs4468255 was significantly correlated with IDCM of Chinese Han population. A allele of rs4468255 is higher in IDCM patients with ICD implantation, suggesting the influence of genetic background in the generation of this response. In addition, rs11812601, rs56165849, and rs3740346 in LDB3 show association with brain natriuretic peptide, DBP, and LVEF levels in patients with IDCM but did not show any association with IDCM susceptibility.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adaptor Proteins, Signal Transducing/genetics , Alleles , Asian People , Cardiomyopathy, Dilated/surgery , China/epidemiology , Defibrillators, Implantable , Exons , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , LIM Domain Proteins/genetics , Linkage Disequilibrium , Mutation , Polymorphism, Genetic , Sequence Analysis, DNAABSTRACT
<p><b>OBJECTIVE</b>To examine the hemodynamic and electrophysiological influence of left ventricular aneurysm (LVA) formation in patients with idiopathic dilated cardiomyopathy (IDCM).</p><p><b>METHODS</b>All hospital records were retrospectively reviewed from IDCM patients admitted to our hospital between 2003 and 2008. Patients with coronary angiography evidenced ischemic cardiomyopathy were excluded. IDCM patients with LVA (I + L) diagnosed by left ventriculography were enrolled. Twelve age-, gender- and left-ventricular-diameter- matched patients with IDCM without LVA served as control group (I - L).</p><p><b>RESULTS</b>Six out of 998 patients with IDCM were confirmed to have LVA (0.60%). The LV peak-systolic pressure was higher in the I + L group than in I - L group [ (130 +/- 10) mm Hg (1 mm Hg = 0.133 kPa) vs. (117 +/-9) mm Hg, P < 0.05]. The LV end-diastolic volume was significantly larger in the I + L group than in I-L group[ (272 +/- 57) ml vs. (207 +/- 60) ml, P < 0.05]. The LV ejection fraction was slightly lower in the I + L group than in I - L group [ (27 +/- 9)% vs. (35 +/- 6)%, P = 0. 09]. Ventricular arrhythmia occurred more frequently in I + L group than in I - L group.</p><p><b>CONCLUSION</b>LVA formation in IDCM was a rare phenomenon. IDCM patients with LVA seem to have higher LV peak-systolic pressure, larger end-diastolic volume, worse LV systolic function and more frequent ventricular arrhythmia than those without LVA.</p>