Abstract 13554: Variations in MiRNAs Regulating Cardiac Growth are Not Common Cause of Hypertrophic Cardiomyopathy
Background: Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by increased wall thickness, diastolic dysfunction and increased risk of arrhythmias, heart failure and stroke. It is mostly caused by mutations in genes coding for heart sarcomere proteins, which can be detected in up to 60% of HCM patients. Micro RNAs (miRNAs) are small non-coding RNAs with an important role in regulation of gene expression. There is growing evidence of their importance in regulation of the cardiac growth, development and hypertrophy. The main purpose of the present study was to evaluate a potential association of miRNA sequence variations with HCM.
Methods: We performed genetic testing in 56 patients with hypertrophic cardiomyopathy, which were negative for causative mutation in 4 genes for sarcomeric proteins (MYBPC3, MYH7, TNNT2, TNNI3) and 60 healthy volunteers. The coding and adjacent regions (120-220nt) of selected miRNAs were analyzed for a presence of sequence variations. The tested panel consisted of miRNA 1-1, miRNA1-2, miRNA 133a1, miRNA 133a2, miRNA 208a, miRNA 208b, miRNA 302a, miRNA 302c, miRNA 367, miRNA 499a and miRNA 499b. The testing was based on PCR amplification of coding miRNA DNA and a subsequent PCR fragment analysis by denaturing capillary electrophoresis (DCE) revealing presence of any variation within the target region.
Results: A total of 3 different variants were detected among the 11 miRNA target regions tested. Those included known polymorphisms rs45489294 in miRNA 208b, rs13136737 in miRNA 367 and rs9989532 in miRNA 1-2, all located in pre-miRNA flanking regions. In the patient group the most frequent polymorphism was in miRNA 208b (10x) followed by miRNA 367 (7x). Both polymorphisms were found with similar frequencies in the group of healthy controls. The remaining detected variation (in miRNA 1-2) was not present in the healthy controls.
Conclusion: Sequence variants in tested miRNAs were rare with allelic frequencies below 10%. Two out of three detected variations were present in both, patient as well as control group. The only variation not observed among healthy controls was miRNA 1-2 rs9989532 found in one patient. Its potential implication in HCM is under further investigation mainly through family pedigree analysis.
- © 2013 by American Heart Association, Inc.