Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder
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-nu...
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MDPI AG
2023-09-01
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| author | Piotr Czarny Sylwia Ziółkowska Łukasz Kołodziej Cezary Watała Paulina Wigner-Jeziorska Katarzyna Bliźniewska-Kowalska Katarzyna Wachowska Małgorzata Gałecka Ewelina Synowiec Piotr Gałecki Michał Bijak Janusz Szemraj Tomasz Śliwiński |
| author_facet | Piotr Czarny Sylwia Ziółkowska Łukasz Kołodziej Cezary Watała Paulina Wigner-Jeziorska Katarzyna Bliźniewska-Kowalska Katarzyna Wachowska Małgorzata Gałecka Ewelina Synowiec Piotr Gałecki Michał Bijak Janusz Szemraj Tomasz Śliwiński |
| author_sort | Piotr Czarny |
| collection | DOAJ |
| description | 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: <i>EXOG</i> c.-188T > G (rs9838614), <i>EXOG</i> c.*627G > A (rs1065800), <i>POLG</i> c.-1370T > A (rs1054875), <i>ENDOG</i> c.-394T > C (rs2977998) and <i>ENDOG</i> c.-220C > T (rs2997922), while genotyping was performed on 538 DNA samples (277 cases and 261 controls) using TaqMan probes. All SNPs of <i>EXOG</i> and <i>ENDOG</i> 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 <i>POLG</i> 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. |
| first_indexed | 2024-03-09T13:52:51Z |
| format | Article |
| id | doaj.art-3bc4b835c964414897b960bbafadf0ba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:52:51Z |
| publishDate | 2023-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3bc4b835c964414897b960bbafadf0ba2023-11-30T20:46:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191475210.3390/ijms241914752Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive DisorderPiotr Czarny0Sylwia Ziółkowska1Łukasz Kołodziej2Cezary Watała3Paulina Wigner-Jeziorska4Katarzyna Bliźniewska-Kowalska5Katarzyna Wachowska6Małgorzata Gałecka7Ewelina Synowiec8Piotr Gałecki9Michał Bijak10Janusz Szemraj11Tomasz Śliwiński12Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandLaboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 92-215 Lodz, PolandDepartment of Haemostatic Disorders, Medical University of Lodz, 92-215 Lodz, PolandDepartment of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-136 Lodz, PolandDepartment of Adult Psychiatry, Medical University of Lodz, 91-229 Lodz, PolandDepartment of Adult Psychiatry, Medical University of Lodz, 91-229 Lodz, PolandDepartment of Psychotherapy, Medical University of Lodz, 91-229 Lodz, PolandLaboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 92-215 Lodz, PolandDepartment of Adult Psychiatry, Medical University of Lodz, 91-229 Lodz, PolandBiohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, 90-136 Lodz, PolandDepartment of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, PolandLaboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 92-215 Lodz, PolandOne 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: <i>EXOG</i> c.-188T > G (rs9838614), <i>EXOG</i> c.*627G > A (rs1065800), <i>POLG</i> c.-1370T > A (rs1054875), <i>ENDOG</i> c.-394T > C (rs2977998) and <i>ENDOG</i> c.-220C > T (rs2997922), while genotyping was performed on 538 DNA samples (277 cases and 261 controls) using TaqMan probes. All SNPs of <i>EXOG</i> and <i>ENDOG</i> 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 <i>POLG</i> 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.https://www.mdpi.com/1422-0067/24/19/14752oxidative stressdepressionDNA repairDNA damagemitochondrial DNAgene polymorphism |
| spellingShingle | Piotr Czarny Sylwia Ziółkowska Łukasz Kołodziej Cezary Watała Paulina Wigner-Jeziorska Katarzyna Bliźniewska-Kowalska Katarzyna Wachowska Małgorzata Gałecka Ewelina Synowiec Piotr Gałecki Michał Bijak Janusz Szemraj Tomasz Śliwiński Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder International Journal of Molecular Sciences oxidative stress depression DNA repair DNA damage mitochondrial DNA gene polymorphism |
| title | Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder |
| title_full | Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder |
| title_fullStr | Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder |
| title_full_unstemmed | Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder |
| title_short | Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder |
| title_sort | single nucleotide polymorphisms in genes maintaining the stability of mitochondrial dna affect the occurrence onset severity and treatment of major depressive disorder |
| topic | oxidative stress depression DNA repair DNA damage mitochondrial DNA gene polymorphism |
| url | https://www.mdpi.com/1422-0067/24/19/14752 |
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