Investigation of Polymorphisms in Non-Coding Region of Human Mitochondrial DNA in 31 Iranian Hypertrophic Cardiomyopathy (HCM) Patients

Document Type : Research Paper


1 Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, P.O. Box 14155-6343, Tehran, I.R. Iran.

2 Iran University of Medical Sciences, Shaheed Rajaei Cardiovascular Medical Center, Tehran, Iran.

3 Russian Research Center of Medical Genetics, Laboratory of DNA Research, Moscow, Russia.


The D-loop region is a hot spot for mitochondrial DNA (mtDNA) alterations, containing two hypervariable segments, HVS-I and HVS-II. In order to identify polymorphic sites and potential genetic background accounting for Hypertrophic CardioMyopathy (HCM) disease, the complete non-coding region of mtDNA from 31 unrelated HCM patients and 45 normal controls were sequenced. The sequences were aligned upon the revised Cambridge Reference Sequence (rCRS) and any incompatibilities were recorded as numerical changes in homoPolymeric C Tract (PCT), single base substitutions, insertions and deletions (Indels). Nucleotide substitutions were found to make up the majority of the mutations, rather than indels. We drew significantly
high transition rate (81.8%) versus lower frequency of transversions (18.2%). 12 polymorphisms were identified in this study which had not been published in the MitoMap database. PCT changes at position 303-309 were detected in 83% of our samples. Our results suggest that an increased level of HVS-I and HVS-II substitutions may be an indicator of mitochondrial DNA instability. Furthermore, mtDNA mutations
may play an important role in pathogenesis of cardiac arrest which has remained unexplained for long.