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MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome.

Hedley, PL; Carlsen, AL; Christiansen, KM; Kanters, JK; Behr, ER; Corfield, VA; Christiansen, M (2014) MicroRNAs in cardiac arrhythmia: DNA sequence variation of MiR-1 and MiR-133A in long QT syndrome. Scandinavian Journal of Clinical and Laboratory Investigation, 74 (6). pp. 485-491. ISSN 1502-7686 https://doi.org/10.3109/00365513.2014.905696
SGUL Authors: Behr, Elijah Raphael

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Abstract

Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within messenger RNAs (mRNAs). The human genome encodes over 1800 miRNAs, which target about 60% of human genes. Consequently, miRNAs are likely to regulate many complex processes in the body, indeed aberrant expression of various miRNA species has been implicated in numerous disease states, including cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain some cases of LQTS. Four miRNA genes (miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2), which encode MiR-1 and MiR-133A, were sequenced in 125 LQTS probands. No genetic variants were identified in miR-1-1 or miR-133a-1; but in miR-1-2 we identified a single substitution (n.100A> G) and in miR-133a-2 we identified two substitutions (n.-19G> A and n.98C> T). None of the variants affect the mature miRNA products. Our findings indicate that sequence variants of miR-1-1, miR-1-2, miR-133a-1 and miR-133a-2 are not a cause of LQTS in this cohort.

Item Type: Article
Additional Information: © 2014 Informa Healthcare. Made available with permission from the publisher.
Keywords: DNA mutational analysis, gene expression regulation, long QT syndrome, single nucleotide polymorphism, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cardiac (INCCCA)
Journal or Publication Title: Scandinavian Journal of Clinical and Laboratory Investigation
ISSN: 1502-7686
Language: eng
Dates:
DateEvent
September 2014Published
PubMed ID: 24809446
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107314
Publisher's version: https://doi.org/10.3109/00365513.2014.905696

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