Relation of ATPase6 Mutations and Telomere Length in Schizophrenia Patients
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Objective: Schizophrenia is a serious mental disorder. Mutations in mitochondrial genes can change energy metabolism. Telomere is a tandem sequence at the end of chromosomes. Shorter telomere length has been shown in schizophrenia. The aim of this study was to determine the relationship between ATPase6 gene mutations and telomere length in schizophrenia patients. Methods: Blood samples of 34 patients and 34 healthy controls were used. In this study conventional PCR, Sanger sequencing technic and real-time PCR were utilized. Results: Five different mutations (A8860G, A8836, G8697A, C8676T, and A8701G) in the ATPase6 gene were identified in schizophrenia patients. The most seen mutation was A8860G (94%). Telomere length analysis indicated the relation of ATPase6 gene mutations and telomere length variations (p = 0.001). Patients carrying the A8860G mutation had shorter telomere lengths than patients carrying other mutations. Comparing telomere length between schizophrenia patients and healthy controls revealed that the mean telomere length of schizophrenia patients was shorter than healthy controls (p = 0.006). The demographic analysis demonstrated a significant relationship between marital status and telomere length (p = 0.011). Besides that, the duration of the illness is another factor that impacts telomere length (p = 0.044). There is no significant relation between telomere length and other clinical and demographic characteristics including education status, age, gender, etc. Conclusion: In conclusion, telomere length and ATPase6 gene mutations have a significant relation. Studies with larger patient populations and investigation of other mitochondrial gene mutations will make the clearer link between telomere length and mitochondrial mutations.
Abstract
Objective: Schizophrenia is a serious mental disorder. Mutations in mitochondrial genes can change energy metabolism. Telomere is a tandem sequence at the end of chromosomes. Shorter telomere length has been shown in schizophrenia. The aim of this study was to determine the relationship between ATPase6 gene mutations and telomere length in schizophrenia patients. Methods: Blood samples of 34 patients and 34 healthy controls were used. In this study conventional PCR, Sanger sequencing technic and real-time PCR were utilized. Results: Five different mutations (A8860G, A8836, G8697A, C8676T, and A8701G) in the ATPase6 gene were identified in schizophrenia patients. The most seen mutation was A8860G (94%). Telomere length analysis indicated the relation of ATPase6 gene mutations and telomere length variations (p = 0.001). Patients carrying the A8860G mutation had shorter telomere lengths than patients carrying other mutations. Comparing telomere length between schizophrenia patients and healthy controls revealed that the mean telomere length of schizophrenia patients was shorter than healthy controls (p = 0.006). The demographic analysis demonstrated a significant relationship between marital status and telomere length (p = 0.011). Besides that, the duration of the illness is another factor that impacts telomere length (p = 0.044). There is no significant relation between telomere length and other clinical and demographic characteristics including education status, age, gender, etc. Conclusion: In conclusion, telomere length and ATPase6 gene mutations have a significant relation. Studies with larger patient populations and investigation of other mitochondrial gene mutations will make the clearer link between telomere length and mitochondrial mutations.
참고문헌 (49)
- 이병대, "Heritability and Familiality of Temperament and Character Dimensions in Korean Families with Schizophrenic Linkage Disequilibrium", Clinical Psychopharmacology and Neuroscience, 14(2), pp.203~209 (2016), 대한정신약물학회
- Tsuang MT, "Genes, environment and schizophrenia", Br J Psychiatry Suppl, 40, pp.s18~s24 (2001)
- Rajasekaran A, "Mitochondrial dysfunction in schizophrenia : pathways, mechanisms and implications", Neurosci Biobehav Rev, 48, pp.10~21 (2015)
- Li Z, "The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses", Cell, 119, pp.873~887 (2004)
- Nijtmans LG, "Assembly of mitochondrial ATP synthase in cultured human cells : implications for mitochondrial diseases", Biochim Biophys Acta, 1272, pp.190~198 (1995)
- Wallace DC, "Diseases of the mitochondrial DNA", Annu Rev Biochem, 61, pp.1175~1212 (1992)
- Prabakaran S, "Mitochondrial dysfunction in schizophrenia : evidence for compromised brain metabolism and oxidative stress", Mol Psychiatry, 9, pp.684~697 (2004)
- Altar CA, "Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts", Biol Psychiatry, 58, pp.85~96 (2005)
- Ben-Shachar D, "The interplay between mitochondrial complex I, dopamine and Sp1 in schizophrenia", J Neural Transm(Vienna), 116, pp.1383~1396 (2009)
- Korshunov SS, "High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria", FEBS Lett, 416, pp.15~18 (1997)
- Sohal RS, "Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse", Mech Ageing Dev, 74, pp.121~133 (1994)
- Oikawa S, "Site-specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening", FEBS Lett, 453, pp.365~368 (1999)
- Aubert G, "Telomeres and aging", Physiol Rev, 88, pp.557~579 (2008)
- Hemann MT, "The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability", Cell, 107, pp.67~77 (2001)
- Epel ES, "Accelerated telomere shortening in response to life stress", Proc Natl Acad Sci U S A, 101, pp.17312~17315 (2004)
- Simon NM, "Telomere shortening and mood disorders : preliminary support for a chronic stress model of accelerated aging", Biol Psychiatry, 60, pp.432~435 (2006)
- Kao HT, "Rapid telomere erosion in schizophrenia", Mol Psychiatry, 13, pp.118~119 (2008)
- Mirabello L, "The association between leukocyte telomere length and cigarette smoking, dietary and physical variables, and risk of prostate cancer", Aging Cell, 8, pp.405~413 (2009)
- American Psychiatric Association, "Diagnostic and statistical manual of mental disorders : DSM-5" (2013), American Psychiatric Association
- Gil ME, "Real-time quantitative PCR of telomere length", Mol Biotechnol, 27, pp.169~172 (2004)
- Kay SR, "The positive and negative syndrome scale(PANSS)for schizophrenia", Schizophr Bull, 13, pp.261~276 (1987)
- Guy W, "ECDEU assessment manual for psychopharmacology" (1976), Department of Health, Education, and Welfare
- Mortimer AM, "Symptom rating scales and outcome in schizophrenia", Br J Psychiatry Suppl, 50, pp.s7~s14 (2007)
- Overall JE, "The brief psychiatric rating scale", Psychol Rep, 10, pp.799~812 (1962)
- Sahin E, "Telomere dysfunction induces metabolic and mitochondrial compromise", Nature, 470, pp.359~365 (2011)
- Kota LN, "Shortened telomere in unremitted schizophrenia", Psychiatry Clin Neurosci, 69, pp.292~297 (2015)
- Rao S, "Accelerated leukocyte telomere erosion in schizophrenia : evidence from the present study and a meta-analysis", J Psychiatr Res, 79, pp.50~56 (2016)
- van Mierlo HC, "Telomere quantification in frontal and temporal brain tissue of patients with schizophrenia", J Psychiatr Res, 95, pp.231~234 (2017)
- Galletly C, "Shorter telomere length in people with schizophrenia : a preliminary study from Australia", Schizophr Res, 190, pp.46~51 (2017)
- Monroy-Jaramillo N, "Leukocyte telomere length in Hispanic schizophrenia patients under treatment with olanzapine", J Psychiatr Res, 90, pp.26~30 (2017)
- Bertolin C, "Analysis of complete mitochondrial genomes of patients with schizophrenia and bipolar disorder", J Hum Genet, 56, pp.869~872 (2011)
- Bi R, "Mitochondrial genome variations and functional characterization in Han Chinese families with schizophrenia", Schizophr Res, 171, pp.200~206 (2016)
- Ivanova EM, "NGS-based mtDNA profiling could reveal genetic alterations in schizophrenia", Curr Top Med Chem, 21, pp.938~948 (2021)
- Martorell L, "New variants in the mitochondrial genomes of schizophrenic patients", Eur J Hum Genet, 14, pp.520~528 (2006)
- Ueno H, "Analysis of mitochondrial DNA variants in Japanese patients with schizophrenia", Mitochondrion, 9, pp.385~393 (2009)
- Torrell H, "Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia", Am J Med Genet B Neuropsychiatr Genet, 165B, pp.607~617 (2014)
- Zhang Y, "Longer telomeres in elderly schizophrenia are associated with long-term hospitalization in the Japanese population", J Psychiatr Res, 103, pp.161~166 (2018)
- Nieratschker V, "Longer telomere length in patients with schizophrenia", Schizophr Res, 149, pp.116~120 (2013)
- Maurya PK, "Leukocyte telomere length variation in different stages of schizophrenia", J Psychiatr Res, 96, pp.218~223 (2018)
- Malaspina D, "Telomere length, family history, and paternal age in schizophrenia", Mol Genet Genomic Med, 2, pp.326~331 (2014)
- Yin Cui, "Longer Telomere Length of T lymphocytes in Patients with Early and Chronic Psychosis", Clinical Psychopharmacology and Neuroscience, 15(2), pp.146~152 (2017), 대한정신약물학회[DOI]
- Zhou MC, "Analysis of association among clinical features and shorter leukocyte telomere length in mitochondrial diabetes with m. 3243A>G mitochondrial DNA mutation", BMC Med Genet, 16, pp.92~ (2015)
- Weischer M, "Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake : 4, 576 general population individuals with repeat measurements 10 years apart", PLoS Genet, 10, pp.e1004191~ (2014)
- Balzan RP, "Shorter telomere length in people with schizophrenia who live alone?", Schizophr Res, 199, pp.422~423 (2018)
- Yen YC, "Older adults with higher income or marriage have longer telomeres", Age Ageing, 42, pp.234~239 (2013)
- Pawelczyk T, "Telomere length in blood cells is related to the chronicity, severity, and recurrence rate of schizophrenia", Neuropsychiatr Dis Treat, 11, pp.1493~1503 (2015)
- Polho GB, "Antipsychotics preserve telomere length in peripheral blood mononuclear cells after acute oxidative stress injury", Neural Regen Res, 17, pp.1156~1160 (2022)
- Yu WY, "Short telomeres in patients with chronic schizophrenia who show a poor response to treatment", J Psychiatry Neurosci, 33, pp.244~247 (2008)
- Ather Muneer, "Telomere Biology in Mood Disorders: An Updated, Comprehensive Review of the Literature", Clinical Psychopharmacology and Neuroscience, 17(3), pp.343~363 (2019), 대한정신약물학회[DOI]
