Key result
Circulating miR-499a-5p identifies MYH7 variant carriers in HCM with an AUC of ~0.95.
Why the study?
Hypertrophic cardiomyopathy has significant genetic and phenotypic heterogeneity, requiring novel biomarkers to increase diagnostic accuracy and clarify phenotype formation.
Does circulating miR-499a-5p serve as a biomarker to identify MYH7-associated hypertrophic cardiomyopathy?
Observational (n=76)
Does circulating miR-499a-5p serve as a biomarker to identify MYH7-associated hypertrophic cardiomyopathy?
Effect estimate: AUC 0.95 (95% CI 0.88-1.03)
p-value: p=0.0004
Circulating miR-499a-5p is a highly sensitive and specific potential biomarker for identifying hypertrophic cardiomyopathy caused by pathogenic variants in the MYH7 gene.
May support miR-499a-5p as biomarker for MYH7-HCM; hypothesis-generating and requires prospective validation.
Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disease with significant genetic and phenotypic heterogeneity. To search for novel biomarkers, which could increase the accuracy of HCM diagnosis and improve understanding of its phenotype formation, we analyzed the levels of circulating miRNAs—stable non-coding RNAs involved in post-transcriptional gene regulation. Performed high throughput sequencing of miRNAs in plasma of HCM patients and controls pinpointed miR-499a-5p as one of 35 miRNAs dysregulated in HCM. Further investigation on enlarged groups of individuals showed that its level was higher in carriers of pathogenic/likely pathogenic (P/LP) variants in MYH7 gene compared to controls (fold change, FC = 8.9; p < 0.0001). Just as important, carriers of variants in MYH7 gene were defined with higher miRNA levels than carriers of variants in the MYBPC3 gene (FC = 14.1; p = 0.0003) and other patients (FC = 4.1; p = 0.0008). The receiver operating characteristic analysis analysis showed the ability of miR-499a-5p to identify MYH7 variant carriers with the HCM phenotype with area under the curve value of 0.95 (95% confidence interval: 0.88−1.03, p = 0.0004); sensitivity and specificity were 0.86 and 0.91 (cut-off = 0.0014). Therefore, miR-499a-5p could serve as a circulating biomarker of HCM, caused by P/LP variants in MYH7 gene.
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Baulina et al. (2022) conducted an observational in Hypertrophic Cardiomyopathy (HCM) (n=76). Circulating miR-499a-5p vs. Healthy controls and non-MYH7 HCM variant carriers was evaluated on Identification of MYH7 variant carriers with HCM phenotype (AUC 0.95, 95% CI 0.88-1.03, p=0.0004). Circulating miR-499a-5p demonstrated high diagnostic accuracy for identifying MYH7 variant carriers with hypertrophic cardiomyopathy, yielding an AUC of 0.95.
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