Rare variants in MuRF1 and MuRF2 were more prevalent in HCM patients than controls (MuRF1: 2.2% vs 0.3%, p=0.04; MuRF2: 3.7% vs 0.7%, p=0.007) and associated with greater wall thickness.
Case-Control (n=901)
Are rare variants in MuRF genes associated with hypertrophic cardiomyopathy and its clinical severity?
Rare variants in MuRF1 and MuRF2 are associated with hypertrophic cardiomyopathy and may act as modifier genes leading to more severe clinical manifestations such as increased left ventricular wall thickness.
Absolute Event Rate: 2.2% vs 0.3%
p-value: p=0.04
Modifier genes contribute to the diverse clinical manifestations of hypertrophic cardiomyopathy (HCM), but are still largely unknown. Muscle ring finger (MuRF) proteins are a class of muscle-specific ubiquitin E3-ligases that appear to modulate cardiac mass and function by regulating the ubiquitin-proteasome system. In this study we screened all the three members of the MuRF family, MuRF1, MuRF2 and MuRF3, in 594 unrelated HCM patients and 307 healthy controls by targeted resequencing. Identified rare variants were confirmed by capillary Sanger sequencing. The prevalence of rare variants in both MuRF1 and MuRF2 in HCM patients was higher than that in control subjects (MuRF1 13/594 (2.2%) vs. 1/307 (0.3%), p = 0.04; MuRF2 22/594 (3.7%) vs. 2/307 (0.7%); p = 0.007). Patients with rare variants in MuRF1 or MuRF2 were younger (p = 0.04) and had greater maximum left ventricular wall thickness (p = 0.006) than those without such variants. Mutations in genes encoding sarcomere proteins were present in 19 (55.9%) of the 34 HCM patients with rare variants in MuRF1 and MuRF2. These data strongly supported that rare variants in MuRF1 and MuRF2 are associated with higher penetrance and more severe clinical manifestations of HCM. The findings suggest that dysregulation of the ubiquitin-proteasome system contributes to the pathogenesis of HCM.
Su et al. (Mon,) conducted a case-control in Hypertrophic cardiomyopathy (n=901). Rare variants in MuRF1 and MuRF2 vs. Healthy controls was evaluated on Prevalence of rare variants in MuRF1 (p=0.04). Rare variants in MuRF1 and MuRF2 were more prevalent in HCM patients than controls (MuRF1: 2.2% vs 0.3%, p=0.04; MuRF2: 3.7% vs 0.7%, p=0.007) and associated with greater wall thickness.
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