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The combined effect of nuclear and mitochondrial genomes on the risk of developing multiple sclerosis

https://doi.org/10.14412/2074-2711-2020-1S-15-19

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Abstract

Multiple sclerosis (MS) is a severe chronic CNS disease characterized by autoimmune inflammation, demyelination, and neurodegeneration. The interaction of mitochondrial and nuclear genomes is shown to be important in the formation of a predisposition to many diseases.

Objective: to analyze the association of MS with the carriage of biallelic combinations, including as components the polymorphisms of three genes of mitochondrial DNA (mtDNA) and those of 16 nuclear genes, the products of which are involved in the functioning of the immune system and may participate in the development of autoimmune inflammation in MS; and, if these combinations are identified, to determine the nature of an interaction between their components.

Patients and methods. The investigation enrolled 540 MS patients and 406 control group individuals; all were Russians. The mitochondrial genome was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. APSampler software was used for multilocus association analysis. 

Results and discussion. The investigators identified five biallelic combinations that were associated with MS (p=0.0036–0.022) and possessed protective properties (odds ratio (OR) 0.67–0.75). The mitochondrial component of the identified combinations was the polymorphisms m.4580 (rs28357975), m.13368 (rs3899498), and m.13708 (rs28359178) mtDNA; the nuclear component was CXCR5 (rs523604), TNFRSF1A (rs1800693), and CD86 (rs2255214) gene polymorphisms. The interaction between the components of the identified combinations was additive.

Conclusion. The data obtained in the Russian population suggest that the combined contribution of the mitochondrial and nuclear genomes may affect the risk of developing MS.

About the Authors

M. S. Kozin
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; Federal Center for the Brain and Neurotechnologies, Federal Biomedical Agency of Russia; National Medical Research Center for Cardiology, Ministry of Health of Russia
Russian Federation

Department of Neurology, Neurosurgery, and Medical Genetics;
Department of Neuroimmunology

1, Ostrovityanov St, Moscow 117997, Russia;
1, Ostrovityanov St, Build. 10, Moscow 117997, Russia;
15A, Third Cherepkovskaya St., Moscow 121552, Russia



I. S. Kiselev
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; National Medical Research Center for Cardiology, Ministry of Health of Russia
Russian Federation

Department of Neurology, Neurosurgery, and Medical Genetics

1, Ostrovityanov St, Moscow 117997, Russia;
15A, Third Cherepkovskaya St., Moscow 121552, Russia



A. N. Boyko
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; Federal Center for the Brain and Neurotechnologies, Federal Biomedical Agency of Russia;
Russian Federation

Department of Neurology, Neurosurgery, and Medical Genetics; 
Department of Neuroimmunology

1, Ostrovityanov St, Moscow 117997, Russia;
1, Ostrovityanov St, Build. 10, Moscow 117997, Russia



O. G. Kulakova
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; National Medical Research Center for Cardiology, Ministry of Health of Russia
Russian Federation

Department of Neurology, Neurosurgery, and Medical Genetics

1, Ostrovityanov St, Moscow 117997, Russia;
15A, Third Cherepkovskaya St., Moscow 121552, Russia



O. O. Favorova
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia; National Medical Research Center for Cardiology, Ministry of Health of Russia
Russian Federation

Department of Neurology, Neurosurgery, and Medical Genetics

1, Ostrovityanov St, Moscow 117997, Russia;
15A, Third Cherepkovskaya St., Moscow 121552, Russia



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For citation:


Kozin M.S., Kiselev I.S., Boyko A.N., Kulakova O.G., Favorova O.O. The combined effect of nuclear and mitochondrial genomes on the risk of developing multiple sclerosis. Neurology, Neuropsychiatry, Psychosomatics. 2020;12(1S):15-19. https://doi.org/10.14412/2074-2711-2020-1S-15-19

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ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)