Variants in miRNA Regulating Cardiac Growth Are Not a Common Cause of Hypertrophic Cardiomyopathy

Abstract

Objectives: A substantial proportion of patients with hypertrophic cardiomyopathy (HCM) do not have causative mutations in the genes for heart sarcomere. The purpose of this study was to evaluate the association between microRNA (miRNA) sequence variants and HCM. Methods: We performed genetic testing on 56 HCM patients who had previously been found to be negative for mutations in the 4 major genes for sarcomeric proteins. The coding and adjacent regions (120-220 nt) of selected miRNAs were analyzed for the presence of sequence variants. The testing was based on PCR amplification of DNA-encoding miRNAs and subsequent denaturing capillary electrophoresis. Results: A total of 3 different variants were detected in the 11 selected miRNAs. These included polymorphisms rs45489294 in miRNA 208b, rs13136737 in miRNA 367 and rs9989532 in miRNA 1-2. In the patient group, the most frequent polymorphism was in miRNA 208b (10 times) followed by miRNA 367 (7 times). Both polymorphisms were found to occur with similar frequencies in the group of healthy controls. The remaining detected variant was not present in the control group, but was not connected with the HCM phenotype in the children of the probands. Conclusion: Sequence variants in miRNAs of patients with HCM are not frequent and the contribution of these variants to the development of this disease was not demonstrated.

Genetic polymorphisms associated with heart failure: A literature review

“…57 HCM patients and healthy controls had similar frequencies of the polymorphisms rs45489294 in miRNA 208b and rs13136737 in miRNA 367. 58 However, re998532 in miRNA 1-2, the only variant not detected in the healthy controls, was a rare SNP but not necessarily an HCMassociated mutation. 58…”

“…58 However, re998532 in miRNA 1-2, the only variant not detected in the healthy controls, was a rare SNP but not necessarily an HCMassociated mutation. 58…”

Inherited Cardiomyopathies and the Role of Mutations in Non-coding Regions of the Genome

“…A later study investigated the presence of miRNA gene variants in HCM patients. In that study, 56 patients with HCM who were screened for the absence of mutations in 4 known genes associated with HCM (MYH7, MYBPC3, TNNT2 , and TNNI3 ) and the absence of other comorbidities that usually result in diastolic dysfunction (like hypertension or valvular diseases) were tested for the presence of mutations in 11 different miRNA genes ( 53 ). Three known single nucleotide variants were identified on 3 different genes: rs45489294 (C>A with minor allele A) in the miRNA 208b gene, rs13136737 (C>A with minor allele A) in the miRNA 367 gene and rs9989532 (A>G with minor allele G) in the miRNA 1-2 gene.…”