Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder
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Published:2023-09-29
Issue:19
Volume:24
Page:14752
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Czarny Piotr1ORCID, Ziółkowska Sylwia1ORCID, Kołodziej Łukasz2ORCID, Watała Cezary3ORCID, Wigner-Jeziorska Paulina4ORCID, Bliźniewska-Kowalska Katarzyna5ORCID, Wachowska Katarzyna5ORCID, Gałecka Małgorzata6ORCID, Synowiec Ewelina2, Gałecki Piotr5ORCID, Bijak Michał7ORCID, Szemraj Janusz1ORCID, Śliwiński Tomasz2ORCID
Affiliation:
1. Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland 2. Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 92-215 Lodz, Poland 3. Department of Haemostatic Disorders, Medical University of Lodz, 92-215 Lodz, Poland 4. Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-136 Lodz, Poland 5. Department of Adult Psychiatry, Medical University of Lodz, 91-229 Lodz, Poland 6. Department of Psychotherapy, Medical University of Lodz, 91-229 Lodz, Poland 7. Biohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, 90-136 Lodz, Poland
Abstract
One of the key features of major depressive disorder (MDD, depression) is increased oxidative stress manifested by elevated levels of mtROS, a hallmark of mitochondrial dysfunction, which can arise from mitochondrial DNA (mtDNA) damage. Thus, the current study explores possibility that the single-nucleotide polymorphisms (SNPs) of genes encoding the three enzymes that are thought to be implicated in the replication, repair or degradation of mtDNA, i.e., POLG, ENDOG and EXOG, have an impact on the occurrence, onset, severity and treatment of MDD. Five SNPs were selected: EXOG c.-188T > G (rs9838614), EXOG c.*627G > A (rs1065800), POLG c.-1370T > A (rs1054875), ENDOG c.-394T > C (rs2977998) and ENDOG c.-220C > T (rs2997922), while genotyping was performed on 538 DNA samples (277 cases and 261 controls) using TaqMan probes. All SNPs of EXOG and ENDOG modulated the risk of depression, but the strongest effect was observed for rs1065800, while rs9838614 and rs2977998 indicate that they might influence the severity of symptoms, and, to a lesser extent, treatment effectiveness. Although the SNP located in POLG did not affect occurrence of the disease, the result suggests that it may influence the onset and treatment outcome. These findings further support the hypothesis that mtDNA damage and impairment in its metabolism play a crucial role not only in the development, but also in the treatment of depression.
Funder
National Science Centre
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference117 articles.
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