What is the clinical evidence from this study?

Study design: Case-Control. Population: Diastolic heart failure (n=352). Intervention: SNP rs2290149 minor allele vs. Major allele / non-carriers. Primary outcome: Association with diastolic heart failure (additive model) (OR 2.14, 95% CI 1.25-3.66, p=0.004).

April 17, 2012Open Access

Cardiac Myosin Binding Protein C and MAP-Kinase Activating Death Domain-Containing Gene Polymorphisms and Diastolic Heart Failure

CWCho‐Kai WuHeart Failure & Transplant YHYin-Tsen HuangNational Yang Ming Chiao Tung University JLJen-Kuang LeeNational Taiwan University Hospital

Key Result

The minor allele of SNP rs2290149 was significantly associated with an increased risk of early diastolic heart failure in a Han Chinese population (OR 2.14).

Study Design

Type

Case-Control (n=352)

Multicenter

Yes

Structured PICO

Are MYBPC3 gene polymorphisms associated with diastolic heart failure in a Chinese population?

Population

352 Han Chinese participants, comprising 176 patients with early diastolic heart failure and 176 matched controls, evaluated for genetic polymorphisms in the MYBPC3 and MADD genes.

Exposure

Presence of MYBPC3 gene polymorphisms (12 tagging SNPs including rs2290149)

Comparator

Absence of specific MYBPC3 gene polymorphisms (wild-type/major alleles)

Outcome

Diagnosis of diastolic heart failure (DHF)

The MYBPC3 gene polymorphism rs2290149 is significantly associated with an increased risk of early diastolic heart failure in a Chinese population.

Main Result

Odds Ratio: 2.14 (95% CI 1.25–3.66)

p-value: p=0.004

Limitations

Relatively small sample size
Patients with moderate and severe diastolic heart failure were not included
Further studies of other ethnic populations are needed
Further fine mapping and functional studies are warranted to prove whether the MADD gene is associated with DHF or if the SNP is involved in the regulation of the MYBPC3 gene

Abstract

OBJECTIVE: Myosin 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. METHODS: A 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. RESULTS: In 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). CONCLUSIONS: We identified a SNP (rs2290149) among the tagging SNP set that was significantly associated with early DHF in a Chinese population.

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