Abstract
ObjectiveMyosin binding protein C (MYBPC3) plays a role in ventricular relaxation. The aim of the study was to investigate the association between cardiac myosin binding protein C (MYBPC3) gene polymorphisms and diastolic heart failure (DHF) in a human case-control study.MethodsA total of 352 participants of 1752 consecutive patients from the National Taiwan University Hospital and its affiliated hospital were enrolled. 176 patients diagnosed with DHF confirmed by echocardiography were recruited. Controls were matched 1-to-1 by age, sex, hypertension, diabetes, renal function and medication use. We genotyped 12 single nucleotide polymorphisms (SNPs) according to HapMap Han Chinese Beijing databank across a 40 kb genetic region containing the MYBPC3 gene and the neighboring DNA sequences to capture 100% of haplotype variance in all SNPs with minor allele frequencies ≧5%. We also analyzed associations of these tagging SNPs and haplotypes with DHF and linkage disequilibrium (LD) structure of the MYBPC3 gene.ResultsIn a single locus analysis, SNP rs2290149 was associated with DHF (allele-specific p = 0.004; permuted p = 0.031). The SNP with a minor allele frequency of 9.4%, had an odds ratio 2.14 (95% CI 1.25–3.66; p = 0.004) for the additive model and 2.06 for the autosomal dominant model (GG+GA : AA, 95% CI 1.17–3.63; p = 0.013), corresponding to a population attributable risk fraction of 12.02%. The haplotypes in a LD block of rs2290149 (C-C-G-C) was also significantly associated with DHF (odds ratio 2.10 (1.53–2.89); permuted p = 0.029).ConclusionsWe identified a SNP (rs2290149) among the tagging SNP set that was significantly associated with early DHF in a Chinese population.
Highlights
Heart failure is a common hemodynamic and neurohormonal syndrome, the prevalence of which is increasing as the population ages [1]
We have previously reported on genetic factors that may contribute to the development and prognosis of Diastolic heart failure (DHF) [8,9]
A 25-bp deletion polymorphism in intron 32 of the MYBPC3 gene was identified in south Asians and found to be associated with an increased risk of cardiomyopathy [12]. We investigated if this common deletion variant was present in a Han Chinese population and if the variant was associated with an increased risk of DHF
Summary
Heart failure is a common hemodynamic and neurohormonal syndrome, the prevalence of which is increasing as the population ages [1]. Diastolic heart failure (DHF) and systolic heart failure (SHF) are the two most commonly encountered forms of heart failure in clinical practice. Overt DHF and SHF appear to be two separate syndromes that have distinctive morphologic and functional change characteristics; the signs, symptoms, and prognoses of both syndromes are very similar [2]. Patients with SHF have eccentric left ventricular (LV). Hypertrophy, whereas patients with DHF have concentric LV hypertrophy [3]. The cytoskeletal protein titin, matrix metalloproteinase degradation, and impaired calcium homeostasis have been linked with DHF [4,5,6,7]. We have previously reported on genetic factors that may contribute to the development and prognosis of DHF [8,9]. The precise genetic etiology of DHF remains poorly understood
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