MtDNA mutations linked with left ventricular hypertrophy

Abstract

Aim: In left ventricular hypertrophy (LVH), the heart muscle thickens. One third of individuals with LVH never complain of heart problems. However, such patients have a high risk of sudden death. LVH can be caused by arterial atherosclerotic lesions. The linkage of mtDNA mutations 652insG, m.5178C>A, m.3336T>C, m.14459G>A, 652delG, m.14846G>A, m.1555A>G, m.15059G>A, m.3256C>T, m.12315G>A and m.13513G>A with atherosclerosis was described earlier by our laboratory. The aim of the study was to analyze the linkage of these mtDNA mutations with LVH.

Methods: DNA from white blood cells was isolated using a phenol-chloroform method. PCR-fragments of DNA contained the region of the investigated mutations. The heteroplasmy level of mtDNA mutations was analyzed using a pyrosequencing-based method developed by our laboratory.

Results: We investigated two groups of individuals. One hundred and ninety-four patients with LVH. Two hundred and ten were conventionally healthy. It was found that mtDNA mutation m.5178C>A was significantly associated with LVH. Single nucleotide replacement m.1555A>G was associated with LVH at the level of significance P ≤ 0.1. At the same time m.12315G>A and m.3336T>C were significantly associated with the absence of this pathology. Single nucleotide replacement m.14459G>A was associated with the absence of LVH at the significance level P ≤ 0.1.

Conclusion: MtDNA mutations m.5178C>A and m.1555A>G can be used for molecular genetic assessment of the predisposition of individuals to the occurrence of left ventricular hypertrophy. They can also be used for the family analysis of this pathology. Mutations m.12315G>A, m.3336T>C and m.14459G>A can be used in the development of LVH gene therapy methods.

Keywords

Left ventricular hypertrophy / heteroplasmy level / mutation / mitochondrial genome / mtDNA

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