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Moskaleva P.V.

Voino-Yasenetsky Krasnoyarsk State Medical University

Shnayder N.A.

Bekhterev National Medical Research Center of Psychiatry and Neurology

Nasyrova R.F.

Bekhterev National Medical Research Center of Psychiatry and Neurology

Association of polymorphic variants of DDC (AADC), AANAT and ASMT genes encoding enzymes for melatonin synthesis with the higher risk of neuropsychiatric disorders

Authors:

Moskaleva P.V., Shnayder N.A., Nasyrova R.F.

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To cite this article:

Moskaleva PV, Shnayder NA, Nasyrova RF. Association of polymorphic variants of DDC (AADC), AANAT and ASMT genes encoding enzymes for melatonin synthesis with the higher risk of neuropsychiatric disorders. S.S. Korsakov Journal of Neurology and Psychiatry. 2021;121(5):151‑157. (In Russ.)
https://doi.org/10.17116/jnevro2021121041151

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References:

  1. Iuvone PM, Brown AD, Haque R, Weller J, Zawilska JB, Chaurasia SS, MaM, Klein DC. Retinal melatonin production: role of proteasomal proteolysis in circadian and photic control of arylalkylamine N-acetyltransferase. Invest Ophthalmol Vis Sci. 2002;43(2):564-572. PubMed PMID: 11818405.
  2. Conti A, Conconi S, Hertens E, Skwarlo-Sonta K, Markowska M, Maestroni JM. Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res. 2000;28(4):193-202.  https://doi.org/10.1034/j.1600-079X.2000.280401.x
  3. Aust S, Thalhammer T, Humpeler S, Jäger W, Klimpfinger M, Tucek G, Obrist P, Marktl W, Penner E, Ekmekcioglu C. The melatonin receptor subtype MT1 is expressed in human gallbladder epithelia. J Pineal Res. 2004;36(1):43-48.  https://doi.org/10.1046/j.1600-079X.2003.00095.x
  4. Donohue SJ, Roseboom PH, Illnerova H, Weller JL, Klein DC. Human hydroxyindole-O-methyltransferase: presence of LINE-1 fragment in a cDNA clone and pineal mRNA. DNA Cell Biol. 1993;12:715-727.  https://doi.org/10.1089/dna.1993.12.715
  5. Klein DC, Coon SL, Roseboom PH, Weller JL, Bernard M, Gastel JA, Zatz M, Iuvone PM, Rodriguez IR, Bégay V, Falcón J, Cahill GM, Cassone VM, Baler R. The melatonin rhythm-generating enzyme: molecular regulation of serotonin N-acetyltransferase in the pineal gland. Recent Prog Horm Res. 1997;52:307-358. PubMed PMID: 9238858.
  6. Murugesan A, Rani MRS, Hampson J, Zonjy B, Lacuey N, Faingold CL, Friedman D, Devinsky O, Sainju RK, Schuele S, Diehl B, Nei M, Harper RM, Bateman LM, Richerson G, Lhatoo SD. Serum serotonin levels in patients with epileptic seizures. Epilepsia. 2018;59(6):91-97.  https://doi.org/10.1111/epi.14198
  7. Walther DJ, Peter JU, Bashammakh S, Hortnagl H, Voits M, Fink H, Bader M. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science. 2003;299(5603):76.  https://doi.org/10.1126/science.1078197
  8. Zhang X, Beaulieu JM, Sotnikova TD, Gainetdinov RR, Caron MG. Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science. 2004;305(5681):217.  https://doi.org/10.1126/science.1097540
  9. Finocchiaro LM, Arzt ES, Fernández-Castelo S, Criscuolo M, Finkielman S, Nahmod VE. Serotonin and melatonin synthesis in peripheral blood mononuclear cells: stimulation by interferon-gamma as part of an immunomodulatory pathway. J Interferon Res. 1988;8(6):705-716. PubMed PMID: 3148005.
  10. Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M. Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats. Jpn J Pharmacol. 1982;32(5):803-811.  https://doi.org/10.1254/jjp.32.803
  11. Gao X, Liu J, Gong P, Wang J, Fang W, Yan H, Zhu L, Zhou X. Identifying new susceptibility genes on dopaminergic and serotonergic pathways for the framing effect in decision-making. Soc Cogn Affect Neurosci. 2017;12(9):1534-1544. https://doi.org/10.1093/scan/nsx062
  12. Kyoto Encyclopedia of Genes and Genomes database (KEGG). https://www.genome.jp/kegg
  13. BioGPS. https://biogps.org/#goto=welcome
  14. Sumi-Ichinose C, Ichinose H, Takahashi E, Hori T, Nagatsu T. Molecular cloning of genomic DNA and chromosomal assignment of the gene for human aromatic L-amino acid decarboxylase, the enzyme for catecholamine and serotonin biosynthesis. Biochemistry. 1992;31(8):2229-2238. PubMed PMID: 1540578.
  15. GeneCards. https://www.genecards.org
  16. Coon SL, Mazuruk K, Bernard M, Roseboom PH, Klein DC, Rodriguez IR. The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): structure, chromosomal localization, and tissue expression. Genomics. 1996;34(1):76-84.  https://doi.org/10.1006/geno.1996.0243
  17. Coon SL, Del Olmo E, Young WS 3rd, Klein DC. Melatonin synthesis enzymes in Macaca mulatta: focus on arylalkylamine N-acetyltransferase (EC 2.3.1.87). J Clin Endocrinol Metab. 2002;87(10):4699-4706. https://doi.org/10.1210/jc.2002-020683
  18. Klein DC. Arylalkylamine N-acetyltransferase: “the Timezyme”. J Biol Chem. 2007;282(7):4233-4237. https://doi.org/10.1074/jbc.R600036200
  19. Zilberman-Peled B, Ron B, Gross A, Finberg JP, Gothilf Y. A possible new role for fish retinal serotonin-N-acetyltransferase-1 (AANAT1): Dopamine metabolism. Brain Res. 2006;1073-1074:220-228.  https://doi.org/10.1016/j.brainres.2005.12.028
  20. Klein DC. The 2004 Aschoff/Pittendrigh lecture: Theory of the origin of the pineal gland — a tale of conflict and resolution. J Biol Rhythms. 2004;19(4):264-279.  https://doi.org/10.1177/0748730404267340
  21. Yi H, Donohue SJ, Klein DC, McBride OW. Localization of the hydroxyindole-O-methyltransferase gene to the pseudoautosomal region: implications for mapping of psychiatric disorders. Hum Mol Genet. 1993;2(2):127-131. PubMed PMID: 8098975.
  22. Abeling NG, Bräutigam C, Hoffmann GF, Barth PG, Wevers RA, Jaeken J, Fiumara A, Knust A, van Gennip AH. Pathobiochemical implications of hyperdopaminuria in patients with aromatic L-amino acid decarboxylase deficiency. J Inherit Metab Dis. 2000;23(4):325-328.  https://doi.org/10.1023/A:1005650325003
  23. Brun L, Ngu LH, Keng WT, Ch’ng GS, Choy YS, Hwu WL, Lee WT, Willemsen MA, Verbeek MM, Wassenberg T, Régal L, Orcesi S, Tonduti D, Accorsi P, Testard H, Abdenur JE, Tay S, Allen GF, Heales S, Kern I, Kato M, Burlina A, Manegold C, Hoffmann GF, Blau N. Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency. Neurology. 2010;75(1):64-71.  https://doi.org/10.1212/WNL.0b013e3181e620ae
  24. Online Mendelian Inheritance in Man (OMIM). https://www.omim.org/entry/608643
  25. Corominas R, Sobrido MJ, Ribasés M, Cuenca-León E, Blanco-Arias P, Narberhaus B, Roig M, Leira R, López-González J, Macaya A, Cormand B. Association study of the serotoninergic system in migraine in the Spanish population. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(1):177-184.  https://doi.org/10.1002/ajmg.b.30972
  26. Toma C, Hervás A, Balmaña N, Salgado M, Maristany M, Vilella E, Aguilera F, Orejuela C, Cuscó I, Gallastegui F, Pérez-Jurado LA, Caballero-Andaluz R, Diego-Otero Yd, Guzmán-Alvarez G, Ramos-Quiroga JA, Ribasés M, Bayés M, Cormand B. Neurotransmitter systems and neurotrophic factors in autism: association study of 37 genes suggests involvement of DDC. World J Biol Psychiatry. 2013;14(7):516-527.  https://doi.org/10.3109/15622975.2011.602719
  27. Yu H, Liu J, Yang A, Yang G, Yang W, Lei H, Quan J, Zhang Z. Lack of Association Between Polymorphisms in Dopa Decarboxylase and Dopamine Receptor-1 Genes With Childhood Autism in Chinese Han Population. J Child Neurol. 2016;31(5):560-564.  https://doi.org/10.1177/0883073815601496
  28. Anderson BM, Schnetz-Boutaud NC, Bartlett J, Wotawa AM, Wright HH, Abramson RK, Cuccaro ML, Gilbert JR, Pericak-Vance MA, Haines JL. Examination of association of genes in the serotonin system to autism. Neurogenetics. 2009;10(3):209-216.  https://doi.org/10.1007/s10048-009-0171-7
  29. Ribasés M, Ramos-Quiroga JA, Hervás A, Bosch R, Bielsa A, Gastaminza X, Artigas J, Rodriguez-Ben S, Estivill X, Casas M, Cormand B, Bayés M. Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB. Mol Psychiatry. 2009;14(1):71-85.  https://doi.org/10.1038/sj.mp.4002100
  30. Redenšek S, Flisar D, Kojović M, Gregorič Kramberger M, Georgiev D, Pirtošek Z, Trošt M, Dolžan V. Dopaminergic Pathway Genes Influence Adverse Events Related to Dopaminergic Treatment in Parkinson’s Disease. Front Pharmacol. 2019;10:8.  https://doi.org/10.3389/fphar.2019.00008
  31. Børglum AD, Hampson M, Kjeldsen TE, Muir W, Murray V, Ewald H, Mors O, Blackwood D, Kruse TA. Dopa decarboxylase genotypes may influence age at onset of schizophrenia. Mol Psychiatry. 2001;6(6):712-717.  https://doi.org/10.1038/sj.mp.4000902
  32. Zhang B, Jia Y, Yuan Y, Yu X, Xu Q, Shen Y, Shen Y. No association between polymorphisms in the DDC gene and paranoid schizophrenia in a northern Chinese population. Psychiatr Genet. 2004;14(3):161-163. PubMed PMID: 15318031.
  33. Young SN. How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci. 2007;32(6):394-399. PubMed PMID: 18043762.
  34. Costas J, Gratacòs M, Escaramís G, Martín-Santos R, de Diego Y, Baca-García E, Canellas F, Estivill X, Guillamat R, Guitart M, Gutiérrez-Zotes A, García-Esteve L, Mayoral F, Moltó MD, Phillips C, Roca M, Carracedo A, Vilella E, Sanjuán J. Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women. J Psychiatr Res. 2010;44(11):717-724.  https://doi.org/10.1016/j.jpsychires.2009.12.012
  35. Ivanov MV. Fluvoxamine: Opportunities in drug therapy psychiatric disorders. Obozrenie psikhiatrii i meditsinskoj psikhologii im. V.M. Bekhtereva. 2012;4:91-96. (In Russ.).
  36. Børglum AD, Bruun TG, Kjeldsen TE, Ewald H, Mors O, Kirov G, Russ C, Freeman B, Collier DA, Kruse TA. Two novel variants in the DOPA decarboxylase gene: association with bipolar affective disorder. Mol Psychiatry. 1999;4(6):545-551. PubMed PMID: 10578236.
  37. Børglum AD, Kirov G, Craddock N, Mors O, Muir W, Murray V, McKee I, Collier DA, Ewald H, Owen MJ, Blackwood D, Kruse TA. Possible parent-of-origin effect of Dopa decarboxylase in susceptibility to bipolar affective disorder. Am J Med Genet B Neuropsychiatr Genet. 2003;117B(1):18-22.  https://doi.org/10.1002/ajmg.b.10030
  38. Hohjoh H, Takasu M, Shishikura K, Takahashi Y, Honda Y, Tokunaga K. Significant association of the arylalkylamine N-acetyltransferase (AA-NAT) gene with delayed sleep phase syndrome. Neurogenetics. 2003;4(3):151-153.  https://doi.org/10.1007/s10048-002-0141-9
  39. Pereira DS, Pedrazzoli M, Koike Bdel V, Louzada FM, Benedito-Silva AA, Lopez AR, Tufik S. The G619A Aa-nat gene polymorphism does not contribute to sleep time variation in the Brazilian population. Behav Genet. 2007;37(4):637-638.  https://doi.org/10.1007/s10519-007-9155-2
  40. Soria V, Martínez-Amorós E, Escaramís G, Valero J, Crespo JM, Gutiérrez-Zotes A, Bayés M, Martorell L, Vilella E, Estivill X, Menchón JM, Gratacòs M, Urretavizcaya M. Resequencing and association analysis of arylalkylamine N-acetyltransferase (AANAT) gene and its contribution to major depression susceptibility. J Pineal Res. 2010;49(1):35-44.  https://doi.org/10.1111/j.1600-079X.2010.00763.x
  41. Gałecki P, Szemraj J, Bartosz G, Bieńkiewicz M, Gałecka E, Florkowski A, Lewiński A, Karbownik-Lewińska M. Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder. J Pineal Res. 2010;48(4):311-317.  https://doi.org/10.1111/j.1600-079X.2010.00754.x
  42. Kripke DF, Nievergelt CM, Tranah GJ, Murray SS, McCarthy MJ, Rex KM, Parimi N, Kelsoe JR. Polymorphisms in melatonin synthesis pathways: possible influences on depression. J Circadian Rhythms. 2011;9:8.  https://doi.org/10.1186/1740-3391-9-8
  43. Melke J, Goubran Botros H, Chaste P, Betancur C, Nygren G, Anckarsäter H, Rastam M, Ståhlberg O, Gillberg IC, Delorme R, Chabane N, Mouren-Simeoni MC, Fauchereau F, Durand CM, Chevalier F, Drouot X, Collet C, Launay JM, Leboyer M, Gillberg C, Bourgeron T. Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry. 2008;13(1):90-98.  https://doi.org/10.1038/sj.mp.4002016

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