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Exp Mol Pathol. 2015 Aug;99(1):25-32. doi: 10.1016/j.yexmp.2015.04.003. Epub 2015 Apr 21.

Association of mutations in the mitochondrial genome with the subclinical carotid atherosclerosis in women.

Author information

1
Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow, Russian Federation; Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.
2
Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, Moscow, Russian Federation.
3
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation; Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, Australia; School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia. Electronic address: y.bobryshev@unsw.edu.au.
4
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation; Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow Region, Russian Federation; Department of Biophysics, Biological Faculty, Moscow State University, Moscow, Russian Federation.

Abstract

The importance of the study of an association of mitochondrial DNA mutations with asymptomatic atherosclerosis in women is undeniable. In the present study, a series of PCR with primers for mutation region and further amplificate pyrosequencing were carried out to identify point substitutions or microdeletions of the mitochondrial genome. The results obtained were processed using the original method of estimating the level of heteroplasmy. Five mutations in the mitochondrial genome, namely C3256T, G14709A, G12315A, G13513A and G14846A, in which the heteroplasmy level was associated with the degree of preclinical atherosclerosis in women, were identified. The data obtained in the study showed that C3256T, G14709A and G12315A mutations have a positive correlation with atherosclerosis while G13513A and G14846A mutations have a negative correlation with atherosclerotic lesions. Total mutational load of the mitochondrial genome for C3256T, G14709A, G12315A, G13513A and G14846A mutations explains 68% of the variability of thickness of the carotid intima-medial layer, while the complex of traditional risk factors for cardiovascular diseases explains only 8% of the IMT variability. Data on the correlation between heteroplasmy levels of C3256T, G14709A, G12315A, G13513A and G14846A mutations prompt a suggestion that these mutations may be present on the same haplotypes of mitochondrial genome, associated with atherosclerosis.

KEYWORDS:

Atherosclerosis; Heteroplasmy level; Mitochondria; Mitochondrial genome; Mutations

PMID:
25910413
DOI:
10.1016/j.yexmp.2015.04.003
[Indexed for MEDLINE]

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