Iranian
Biomedical Journal
Volume 26, Issue 2 (3-2022)
IBJ 2022, 26(2): 110-115 |
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Aghabozorg Afjeh S S, Shams J, Hamednia S, Boshehri B, Amini A, Omrani A et al . Validating MARK2 Gene Polymorphism as a Predictor of Response to Lithium Treatment in Bipolar Patients. IBJ 2022; 26 (2) :110-115
URL: http://ibj.pasteur.ac.ir/article-1-3629-en.html
URL: http://ibj.pasteur.ac.ir/article-1-3629-en.html
Sara Sadat Aghabozorg Afjeh 
, Jamal Shams , Safar Hamednia , Behzad Boshehri , Asmaolhosna Amini , Amin Omrani , Mir Davood Omrani
, Jamal Shams , Safar Hamednia , Behzad Boshehri , Asmaolhosna Amini , Amin Omrani , Mir Davood Omrani
Abstract:
Background: Lithium is a therapeutic option for the treatment of the acute phase of the bipolar disorder and long-term management of this disorder. However, it is estimated that 10 to 60% of patients do not properly response to this medication.
Methods: To investigate the role of MARK2 gene in response to lithium, we genotyped the MARK2 rs10792421 polymorphism in Iranian bipolar patients using amplification Refractory Mutation System-PCR.
Results: Results of this study showed a significant association of this polymorphism with response to lithium. The A allele was more frequent in the responder than the non-responder group and also in the semi- responder group compared to the non-responder group in the codominant model of analysis. AA and AG genotypes were more frequent in both the responder and semi-responder groups compared to the non-responder group in dominant model of analysis.
Conclusion: Based on the findings of the current study, the rs10792421 variant of MARK2 gene could be considered as a potential biomarker for predicting the treatment outcome of bipolar disorder type 1 in Iranian population.
Methods: To investigate the role of MARK2 gene in response to lithium, we genotyped the MARK2 rs10792421 polymorphism in Iranian bipolar patients using amplification Refractory Mutation System-PCR.
Results: Results of this study showed a significant association of this polymorphism with response to lithium. The A allele was more frequent in the responder than the non-responder group and also in the semi- responder group compared to the non-responder group in the codominant model of analysis. AA and AG genotypes were more frequent in both the responder and semi-responder groups compared to the non-responder group in dominant model of analysis.
Conclusion: Based on the findings of the current study, the rs10792421 variant of MARK2 gene could be considered as a potential biomarker for predicting the treatment outcome of bipolar disorder type 1 in Iranian population.
Type of Study: Full Length/Original Article |
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References
1. Cade J F J. Lithium salts in the treatment of psychotic excitement. The medical journal of Australia 1949; 2(10): 349-s2. [DOI:10.5694/j.1326-5377.1949.tb36912.x]
2. Nivoli AM, Colom F, Murru A, Pacchiarotti I, Castro-Loli P, González-Pinto A, Fountoulakis KN, Vieta E. New treatment guidelines for acute bipolar depression: a systematic review. Journal of affective disorders 2011; 129(1-3): 14-26. [DOI:10.1016/j.jad.2010.05.018]
3. Moreira J, Noé G, Rangarajan S, Courtin C, Etain B, Geoffroy PA, Laplanche JL, Vidal M, Bellivier F, Marie-Claire C. Lithium effects on serine-threonine kinases activity: High throughput kinomic profiling of lymphoblastoid cell lines from excellent-responders and non-responders bipolar patients. The world journal of biological psychiatry 2020; 21(4): 317-324. [DOI:10.1080/15622975.2018.1487078]
4. Suppes T, Baldessarini RJ, Faedda GL, Tohen. Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. Archives of general psychiatry 1991; 48(12): 1082-1088. [DOI:10.1001/archpsyc.1991.01810360046007]
5. Goodwin GM. Recurrence of mania after lithium withdrawal. Implications for the use of lithium in the treatment of bipolar affective disorder. The British journal of psychiatry 1994; 164(2): 149-152. [DOI:10.1192/bjp.164.2.149]
6. Jawad I, Watson S, Haddad PM, Talbot PS, McAllister-Williams RH. Medication nonadherence in bipolar disorder: a narrative review. The rapeutic advances in psychopharmacology 2018; 8(12): 349-363. [DOI:10.1177/2045125318804364]
7. Ahmed S, Zhou Z, Zhou J, Chen SQ. Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine. Genomics, proteomics and bioinformatics 2016; 14(5): 298-313. [DOI:10.1016/j.gpb.2016.03.008]
8. Machado-Vieira R, Manji HK, Zarate CA Jr. The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar disorders 2009; 2(Suppl 2): 92-109. [DOI:10.1111/j.1399-5618.2009.00714.x]
9. Forlenza OV, De-Paula VJ, Diniz BS. Neuroprotective effects of lithium: implications for the treatment of Alzheimer's disease and related neurodegenerative disorders. ACS chemical neuroscience 2014; 5(6): 443-450. [DOI:10.1021/cn5000309]
10. Drange OK, Smeland OB, Shadrin AA, Finseth PI, Witoelar A, Frei O. Psychiatric Genomics Consortium Bipolar Disorder Working Group, Wang Y, Hassani S, Djurovic S, Dale AM, Andreassen OA. Genetic overlap between Alzheimer's disease and bipolar disorder implicates the MARK2 and VAC14 genes. Frontiers in neuroscience 2019; 13: 220. [DOI:10.3389/fnins.2019.00220]
11. Pasquali L, Busceti C L, Fulceri F, Paparelli A, Fornai F. Intracellular pathways underlying the effects of lithium. Behavioural pharmacology 2010; 21(5-6): 473-492. [DOI:10.1097/FBP.0b013e32833da5da]
12. Chalecka-Franaszek E, Chuang DM. Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proceedings of the national academy of sciences of the United States of America 1999; 96(15): 8745-8750. [DOI:10.1073/pnas.96.15.8745]
13. Gu GJ, Lund H, Wu D, Blokzijl A, Classon C, von Euler G, Landegren U, Sunnemark D, Kamali-Moghaddam M. Role of individual MARK isoforms in phosphorylation of tau at Ser²⁶² in Alzheimer's disease. Neuromolecular medicine 2013; 15(3): 458-469. [DOI:10.1007/s12017-013-8232-3]
14. Biernat J, Wu YZ, Timm T, Zheng-Fischhofer Q, Mandelkow E, Meijer L, Mandelkow EM. Protein kinase MARK/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity. Molecular biology of the cell 2020; 13: 4013-4028. [DOI:10.1091/mbc.02-03-0046]
15. Martino DJ, Samamé C, Ibañez A, Strejilevich SA. Neurocognitive functioning in the premorbid stage and in the first episode of bipolar disorder: a systematic review. Psychiatry research 2015; 226(1): 23-30. [DOI:10.1016/j.psychres.2014.12.044]
16. Gold CA, Budson AE. Memory loss in Alzheimer's disease: implications for development of therapeutics. Expert review of neurotherapeutics 2008; 8(12):1879-91. [DOI:10.1586/14737175.8.12.1879]
17. Godefroy O, Bakchine S, Verny M, Delabrousse-Mayoux JP, Roussel M, Pere JJ, REFLEX study group. Characteristics of Alzheimer's disease patients with severe executive disorders. Journal of Alzheimers disease 2016; 51(3): 815-825.
18. Matenia D, Mandelkow E M. The tau of MARK: a polarized view of the cytoskeleton. Trends in biochemical sciences 2009; 34(7): 332-342. [DOI:10.1016/j.tibs.2009.03.008]
19. Zhang X, Heng X, Li T, Li L, Yang D, Zhang X, Du Y, Doody RS, Le W. Long-term treatment with lithium alleviates memory deficits and reduces amyloid-beta production in an aged Alzheimer's disease transgenic mouse model. Journal of Alzheimers disease 2011; 24(4): 739-749. [DOI:10.3233/JAD-2011-101875]
20. Matsunaga S, Kishi T, Annas P, Basun H, Hampel H, Iwata N. Lithium as a treatment for Alzheimer's disease: A systematic review and meta-analysis. Journal of Alzheimers disease 2010; 48(2): 403-410. [DOI:10.3233/JAD-150437]
21. Kosuga S, Tashiro E, Kajioka T, Ueki M, Shimizu Y, Imoto M. GSK-3beta directly phosphorylates and activates MARK2/PAR-1. The Journal of biological chemistry 2005; 280(52): 42715-42722. [DOI:10.1074/jbc.M507941200]
22. Kaidanovich-Beilin O, Woodgett JR. GSK-3: Functional Insights from Cell Biology and Animal Models. Frontiers in molecular neuroscience 2011; 4: 40. [DOI:10.3389/fnmol.2011.00040]
23. Hanger DP, Noble W. Functional implications of glycogen synthase kinase-3-mediated tau phosphor-rylation. International journal of Alzheimers disease 2011; 2011: 352805. [DOI:10.4061/2011/352805]
24. Matenia D, Hempp C, Timm T, Eikhof A, Mandelkow EM. Microtubule affinity-regulating kinase 2 (MARK2) turns on phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) at Thr-313, a mutation site in Parkinson disease: effects on mitochondrial transport. The journal of biological chemistry 2012; 287(11): 8174-8186. [DOI:10.1074/jbc.M111.262287]
25. Matenia D, Mandelkow EM. Emerging modes of PINK1 signaling: another task for MARK2. Frontiers in molecular neuroscience 2014; 7: 37. [DOI:10.3389/fnmol.2014.00037]
26. Weihofen A, Thomas KJ, Ostaszewski BL, Cookson MR, Selkoe DJ. Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking. Biochemistry 2009; 48(9): 2045-2052. [DOI:10.1021/bi8019178]
27. Reiner O, Shmueli A, Sapir T. Neuronal migration and neurodegeneration: 2 Sides of the same coin. Cerebral cortex 2009; 19: 42-48. [DOI:10.1093/cercor/bhp039]
28. Wei X, Xu L, Jeddo SF, Li K, Li X, Li J. MARK2 enhances cisplatin resistance via PI3K/AKT/NF-κB signaling pathway in osteosarcoma cells. American journal of translational research 2020; 12(5):1807-1823.
29. Regier DA, Kuhl EA, Kupfer DJ. The DSM-5: classification and criteria changes. World psychiatry 2013; 12(2): 92-98. [DOI:10.1002/wps.20050]
30. Insolera R, Chen S, Shi SH. Par proteins and neuronal polarity. Developmental neurobiology 2011; 71(6): 483-494. [DOI:10.1002/dneu.20867]
31. Kon E, Cossard A, Jossin Y. Neuronal polarity in the embryonic mammalian cerebral cortex. Frontiers in cellular neuroscience 2017; 11: 163. [DOI:10.3389/fncel.2017.00163]
32. Sanches M, Keshavan MS, Brambilla P, Soares JC. Neurodevelopmental basis of bipolar disorder: A critical appraisal. Progress in neuro-psychopharmacology and biological psychiatry 2008; 32(7): 1617-1627. [DOI:10.1016/j.pnpbp.2008.04.017]
33. O'Shea KS, McInnis MG. Neurodevelopmental origins of bipolar disorder: iPSC models. Molecular and cellular neurosciences 2016; 73: 63-83. [DOI:10.1016/j.mcn.2015.11.006]
34. Jack CR Jr, Knopman D S, Jagust W J, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste H J, Weigand SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. The lancet neurology 2013; 12(2): 207-216. [DOI:10.1016/S1474-4422(12)70291-0]
35. Forlenza OV, Aprahamian I, Radanovic M, Talib LL, Camargo MZ, Stella F, Machado-Vieira R, Gattaz WF. Cognitive impairment in late-life bipolar disorder is not associated with Alzheimer's disease pathological signature in the cerebrospinal fluid. Bipolar disorders 2016; 18(1): 63-70. [DOI:10.1111/bdi.12360]
36. Jakobsson J, Pålsson E, Sellgren C, Rydberg F, Ekman A, Zetterberg H, Blennow K, Landén M. CACNA1C polymorphism and altered phosphorylation of tau in bipolar disorder. The British journal of psychiatry 2016; 208(2): 195-196. [DOI:10.1192/bjp.bp.114.159806]
37. Freland L, Beaulieu JM. Inhibition of GSK3 by lithium, from single molecules to signaling networks. Frontiers in molecular neuroscience 2012; 5: 14. [DOI:10.3389/fnmol.2012.00014]
38. Timm T, Balusamy K, Li X, Biernat J, Mandelkow E, Mandelkow E M. Glycogen Synthase Kinase (GSK) 3β directly phosphorylates serine 212 in the regulatory loop and inhibits microtubule affinity-regulating kinase (MARK) 2. The journal of biological chemistry 2008; 2839(27): 18873-18882. [DOI:10.1074/jbc.M706596200]
39. Németh ZH, Deitch EA, Szabó C, Fekete Z, Hauser CJ, Haskó G. Lithium induces NF-kappa B activation and interleukin-8 production in human intestinal epithelial cells. The journal of biological chemistry 2002; 277(10): 7713-7719. [DOI:10.1074/jbc.M109711200]
40. Miklowitz DJ, Portnoff LC, Armstrong CC, Keenan-Miller D., Breen EC, Muscatell K A, Eisenberger N I, Irwin MR. Inflammatory cytokines and nuclear factor-kappa B activation in adolescents with bipolar and major depressive disorders. Psychiatry research 2016; 241: 315-322. [DOI:10.1016/j.psychres.2016.04.120]
41. Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychological bulletin 2014; 140(3): 774-815. [DOI:10.1037/a0035302]
42. Ward LD, Kellis M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic acids research 2012; 40: 930-934. [DOI:10.1093/nar/gkr917]
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