Investigation of polymorphisms in non-coding region of human mitochondrial DNA in 31 Iranian hypertrophic cardiomyopathy [HCM] patients

ABSTRACT

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