World Library  
Flag as Inappropriate
Email this Article

Monoamine oxidase A

Article Id: WHEBN0004048014
Reproduction Date:

Title: Monoamine oxidase A  
Author: World Heritage Encyclopedia
Language: English
Subject: Tetrindole, Dopamine, Monoamine oxidase, Ayahuasca, Esuprone
Collection: Aggression, Ec 1.4.3, Human Proteins
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Monoamine oxidase A

Monoamine oxidase A

Ribbon diagram of an MAO-A outer membrane of a mitochondrion.[1]
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; MAO-A
External IDs ChEMBL: GeneCards:
EC number
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAOA gene.[2][3] Monoamine oxidase A is an isozyme of monoamine oxidase. It preferentially deaminates norepinephrine (noradrenaline), epinephrine (adrenaline), serotonin, and dopamine (which is equally deaminated by MAO-A and MAO-B).

It is inhibited by befloxatone. Inhibition of both MAO-A and MAO-B using a monoamine oxidase inhibitor (MAO inhibitor) is used in the treatment of clinical depression, erectile dysfunction and anxiety.

Contents

  • Function 1
  • Clinical significance 2
  • Aggression and the "Warrior gene" 3
    • Animal studies 3.1
    • Epigenetics 3.2
    • Legal implications 3.3
    • Cancer research 3.4
  • MAO-A inhibitors 4
  • MAO-A inducers 5
  • References 6
  • Further reading 7

Function

Monoamine oxidase A is an enzyme that degrades amine neurotransmitters, such as dopamine, norepinephrine, and serotonin. The protein localizes to the outer mitochondrial membrane. Its encoding gene is adjacent to a related gene (MAOB) on the opposite strand of the X chromosome.

Clinical significance

In humans, there is a 30-base repeat sequence repeated in one of several different numbers of times in the promoter region of the gene coding for MAO-A. There are 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence, with the 3R and 4R variants most common in Caucasians. The 3.5R and 4R variants have been found to be more highly active than 3R or 5R, in a study which did not examine the 2R variant.[4] An association between the 2R allele of the VNTR region of the gene and an increase in the likelihood of committing serious crime or violence has been found.[4][5][6]

MAO-A levels in the brain as measured using positron emission tomography are elevated by an average of 34% in patients with major depressive disorder.[7] Genetic association studies examining the relationship between high-activity MAOA variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females,[8] depressed suicide in males,[9] major depression and sleep disturbance in males[10] and major depressive disorder in both males and females.[11]

Other studies failed to find a significant relationship between high-activity variants of the MAOA gene and major depressive disorder.[12][13] In patients with major depressive disorder, those with MAOA G/T polymorphisms (rs6323) coding for the highest-activity form of the enzyme have a significantly lower magnitude of placebo response than those with other genotypes.[14]

Mutation in the MAOA gene results in monoamine oxidase deficiency, or Brunner syndrome.[15]

Aggression and the "Warrior gene"

A version of the monoamine oxidase-A gene has been popularly referred to as the warrior gene.[16] Several different versions of the gene are found in different individuals, although a functional gene is present in most humans (with the exception of a few individuals with Brunner syndrome).[17] In the variant, the allele associated with behavioural traits is shorter (30 bases) and may produce less MAO-A enzyme.[18] This gene variation is in a regulatory promoter region about 1000 bases from the start of the region that encodes the MAO-A enzyme.

The frequency distribution of variants of the MAO-A gene differs between ethnic groups.[18][19] 59% of Black men, 54% of Chinese men, 56% of Maori men, and 34% of Caucasian men carry the 3R allele. 5.5% of Black men, 0.1% of Caucasian men, and 0.00067% of Asian men carry the 2R allele.[6][18][19][20][21][22][23][24][25][26]

A connection between a version of the monoamine oxidase A gene (3R) and several types of antisocial behavior has been found. MAO-A had no statistically significant main effect on antisocial behavior. Maltreated children with genes causing high levels of MAO-A were less likely to develop antisocial behavior.[27] Low MAO-A activity in combination with abuse experienced during childhood results in an increased risk of aggressive behaviour as an adult.[28] High testosterone, maternal tobacco smoking during pregnancy, poor material living standards, dropping out of school, and low IQ can also trigger violent behavior in men with the low-activity alleles (which are overwhelmingly the 3R allele).[29][30]

In individuals with the low activity MAO-A gene, when faced with social exclusion or ostracism showed higher levels of aggression than individuals with the high activity MAO-A gene.[31] Low activity MAO-A could significantly predict aggressive behaviour in a high provocation situation, but was less associated with aggression in a low provocation situation. Individuals with the low activity variant of the MAO-A gene were just as likely as participants with the high activity variant to retaliate when the loss was small. However, they were more likely to retaliate and with greater force when the loss was large.[32]

“Monoamine oxidases (MAOs) are enzymes that are involved in the breakdown of neurotransmitters such as serotonin and dopamine and are, therefore, capable of influencing feelings, mood, and behaviour of individuals”.[33] According to this, if there was a mutation to the gene that is involved in the process of promoting or inhibiting MAO enzymes, it could affect a person’s personality or behaviour and could therefore make them more prone to aggression. A deficiency in the MAO-A gene has shown higher levels of aggression in males, which could further stimulate more research into this controversial topic. “A deficiency in monoamine oxidase A (MAO-A) has been shown to be associated with aggressive behaviour in men of a Dutch family”.[34] Many more genes may be involved in violent behaviour and environmental factors are also known to have a fundamental role.[16] "Environmental factors," like childhood cognitive ability (IQ), can actually have substantial heritability.[29][35] These findings suggest that further research is needed in this topic of debate.

Animal studies

A dysfunctional MAO-A gene has been correlated with increased aggression levels in mice,[36][37] and has been correlated with heightened levels of aggression in humans.[38] In mice, a dysfunctional MAO-A gene is created through insertional mutagenesis (called ‘Tg8’).[36] Tg8 is a transgenic mouse strain that lacks functional MAO-A enzymatic activity. Mice that lacked a functional MAO-A gene exhibited increased aggression towards intruder mice.[36][39]

Some types of aggression exhibited by these mice were territorial aggression, predatory aggression, and isolation-induced aggression.[37] The MAO-A deficient mice that exhibited increased isolation-induced aggression reveals that an MAO-A deficiency may also contribute to a disruption in social interactions.[40] There is research in both humans and mice to support that a nonsense point mutation in the eighth exon of the MAO-A gene is responsible for impulsive aggressiveness due to a complete MAO-A deficiency.[36][38]

Epigenetics

Epigenetics likely plays an important role in the expression of the MAO-A gene through methylation in women.[41] Studies have linked methylation of the MAO-A gene with nicotine and alcohol dependence in women.[42] A second MAO-A VNTR promoter, P2, influences epigenetic methylation in women only and interacts with having experienced child abuse to influence antisocial personality disorder symptoms, also only in women.[43] Epigenetic methylation of MAO-A in men is very low and with little variability compared to women. It also has a much higher heritability in men than women.[44]

Legal implications

In a 2009 criminal trial in the United States, an argument based on a combination of "warrior gene" and history of child abuse was successfully used to avoid a conviction of first-degree murder and the death penalty; however, the convicted murderer was sentenced to 32 years in prison.[45][46]

Cancer research

MAO-A produces an amine oxidase, which is a class of enzyme known to affect carcinogenesis. Clorgyline, an MAO-A enzyme inhibitor, prevents apoptosis in melanoma cells, in vitro.[47] Cholangiocarcinoma suppresses MAO-A expression, and those patients with higher MAO-A expression had less adjacent organ invasion and better prognosis and survival.[48]

MAO-A inhibitors

MAO-A inducers

References

  1. ^  
  2. ^ Hotamisligil GS, Breakefield XO (August 1991). "Human monoamine oxidase A gene determines levels of enzyme activity". Am. J. Hum. Genet. 49 (2): 383–92.  
  3. ^ Grimsby J, Chen K, Wang LJ, Lan NC, Shih JC (May 1991). "Human monoamine oxidase A and B genes exhibit identical exon-intron organization". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3637–41.  
  4. ^ a b Guo G, Ou XM, Roettger M, Shih JC (May 2008). "The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity". Eur. J. Hum. Genet. 16 (5): 626–34.  
  5. ^ Guo G, Roettger M, Shih JC (August 2008). "The integration of genetic propensities into social-control models of delinquency and violence among male youths". American Sociological Review 73 (4): 543–568.  
  6. ^ a b Beaver KM, et al. (2012). "Exploring the association between the 2-repeat allele of the MAOA gene promoter polymorphism and psychopathic personality traits, arrests, incarceration, and lifetime antisocial behavior". Personality and Individual Differences.  
  7. ^ Meyer JH, Ginovart N, Boovariwala A, Sagrati S, Hussey D, Garcia A, Young T, Praschak-Rieder N, Wilson AA, Houle S (November 2006). "Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression". Arch. Gen. Psychiatry 63 (11): 1209–16.  
  8. ^ Schulze TG, Müller DJ, Krauss H, Scherk H, Ohlraun S, Syagailo YV, Windemuth C, Neidt H, Grässle M, Papassotiropoulos A, Heun R, Nöthen MM, Maier W, Lesch KP, Rietschel M (December 2000). "Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder". Am. J. Med. Genet. 96 (6): 801–3.  
  9. ^ Du L, Faludi G, Palkovits M, Sotonyi P, Bakish D, Hrdina PD (July 2002). "High activity-related allele of MAOA gene associated with depressed suicide in males". NeuroReport 13 (9): 1195–8.  
  10. ^ Du L, Bakish D, Ravindran A, Hrdina PD (September 2004). "MAOA gene polymorphisms are associated with major depression and sleep disturbance in males". NeuroReport 15 (13): 2097–101.  
  11. ^ Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW (September 2005). "Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response". Neuropsychopharmacology 30 (9): 1719–23.  
  12. ^ Serretti A, Cristina S, Lilli R, Cusin C, Lattuada E, Lorenzi C, Corradi B, Grieco G, Costa A, Santorelli F, Barale F, Nappi G, Smeraldi E (May 2002). "Family-based association study of 5-HTTLPR, TPH, MAOA, and DRD4 polymorphisms in mood disorders". Am. J. Med. Genet. 114 (4): 361–9.  
  13. ^ Huang SY, Lin MT, Lin WW, Huang CC, Shy MJ, Lu RB (2009). "Association of monoamine oxidase A (MAOA) polymorphisms and clinical subgroups of major depressive disorders in the Han Chinese population". World J. Biol. Psychiatry 10 (4 Pt 2): 544–51.  
  14. ^ Leuchter AF, McCracken JT, Hunter AM, Cook IA, Alpert JE (August 2009). "Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder". J Clin Psychopharmacol 29 (4): 372–7.  
  15. ^ "Entrez Gene: MAOA monoamine oxidase A". 
  16. ^ a b Hogenboom, Melissa (28 October 2014). "Share this pageEmail Print Share this page". BBC News. Retrieved 2014-11-01. 
  17. ^ Online 'Mendelian Inheritance in Man' (OMIM) MONOAMINE OXIDASE A; MAOA. -309850
  18. ^ a b c Sabol SZ, Hu S, Hamer D (September 1998). "A functional polymorphism in the monoamine oxidase A gene promoter". Hum. Genet. 103 (3): 273–9.  
  19. ^ a b Lea R, Chambers G (2007). "Monoamine oxidase, addiction, and the "warrior" gene hypothesis". N. Z. Med. J. 120 (1250): U2441.  
  20. ^ Lu RB, Lin WW, Lee JF, Ko HC, Shih JC (June 2003). "Neither antisocial personality disorder nor antisocial alcoholism is associated with the MAOA gene in Han Chinese males". Alcohol. Clin. Exp. Res. 27 (6): 889–93.  
  21. ^ Zhang M, Chen X, Way N, Yoshikawa H, Deng H, Ke X, Yu W, Chen P, He C, Chi X, Lu Z (September 2011). "The association between infants' self-regulatory behavior and MAO-A gene polymorphism". Dev Sci 14 (5): 1059–65.  
  22. ^ Zhou Q, Hofer C, Eisenberg N, Reiser M, Spinrad TL, Fabes RA (March 2007). "The developmental trajectories of attention focusing, attentional and behavioral persistence, and externalizing problems during school-age years". Dev Psychol 43 (2): 369–85.  
  23. ^ Chen Sy, Wang J, Yu Gq, Liu W, Pearce D (May 1997). "Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity". J. Biol. Chem. 272 (22): 14087–92.  
  24. ^ Ono H, Shirakawa O, Nishiguchi N, Nishimura A, Nushida H, Ueno Y, Maeda K (April 2002). "No evidence of an association between a functional monoamine oxidase a gene polymorphism and completed suicides". Am. J. Med. Genet. 114 (3): 340–2.  
  25. ^ Wang TJ, Huang SY, Lin WW, Lo HY, Wu PL, Wang YS, Wu YS, Ko HC, Shih JC, Lu RB (January 2007). "Possible interaction between MAO-A and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan". Prog. Neuropsychopharmacol. Biol. Psychiatry 31 (1): 108–14.  
  26. ^ Lee SY, Hahn CY, Lee JF, Huang SY, Chen SL, Kuo PH, Lee IH, Yeh TL, Yang YK, Chen SH, Ko HC, Lu RB (July 2010). "MAOA interacts with the ALDH2 gene in anxiety-depression alcohol dependence". Alcohol. Clin. Exp. Res. 34 (7): 1212–8.  
  27. ^ Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (August 2002). "Role of genotype in the cycle of violence in maltreated children". Science 297 (5582): 851–4.  
  28. ^ Frazzetto G, Di Lorenzo G, Carola V, Proietti L, Sokolowska E, Siracusano A, Gross C, Troisi A (2007). "Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAO-A genotype". PLoS ONE 2 (5): e486.  
  29. ^ a b Fergusson DM, Boden JM, Horwood LJ, Miller A, Kennedy MA (February 2012). "Moderating role of the MAO-A genotype in antisocial behaviour". Br J Psychiatry 200 (2): 116–23.  
  30. ^ Sjöberg RL, Ducci F, Barr CS, Newman TK, Dell'osso L, Virkkunen M, Goldman D (January 2008). "A non-additive interaction of a functional MAOA VNTR and testosterone predicts antisocial behavior". Neuropsychopharmacology 33 (2): 425–30.  
  31. ^ Gallardo-Pujol, D.; Andrés-Pueyo, A.; Maydeu-Olivares, A. (1 November 2012). "genotype, social exclusion and aggression: an experimental test of a gene-environment interaction". Genes, Brain and Behavior: n/a–n/a.  
  32. ^ McDermott R, Tingley D, Cowden J, Frazzetto G, Johnson DD (February 2009). "Monoamine oxidase A gene (MAO-A) predicts behavioral aggression following provocation". Proc. Natl. Acad. Sci. U.S.A. 106 (7): 2118–23.  
  33. ^ Hook GR (2009). Warrior genes" and the disease of being Māori""". MAI Review (2): 1–11. 
  34. ^ Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, Müller U, Aguet M, Babinet C, Shih JC (June 1995). "Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA". Science 268 (5218): 1763–6.  
  35. ^ van Soelen IL, Brouwer RM, van Leeuwen M, Kahn RS, Hulshoff Pol HE, Boomsma DI (April 2011). "Heritability of verbal and performance intelligence in a pediatric longitudinal sample". Twin Research and Human Genetics 14 (2): 119–28.  
  36. ^ a b c d Scott AL, Bortolato M, Chen K, Shih JC (May 2008). "Novel monoamine oxidase A knock out mice with human-like spontaneous mutation". NeuroReport 19 (7): 739–43.  
  37. ^ a b Vishnivetskaya GB, Skrinskaya JA, Seif I, Popova NK (2007). "Effect of MAO-A deficiency on different kinds of aggression and social investigation in mice". Aggress Behav 33 (1): 1–6.  
  38. ^ a b Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (October 1993). "Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A". Science 262 (5133): 578–80.  
  39. ^ Vishnivetskaya, Galina B.; Skrinskaya, Julia A.; Seif, Isabelle; Popova, Nina K. (1 January 2007). "Effect of MAO-A deficiency on different kinds of aggression and social investigation in mice". Aggressive Behavior 33 (1): 1–6.  
  40. ^ Hebebrand J, Klug B (September 1995). "Specification of the phenotype required for men with monoamine oxidase type A deficiency". Hum. Genet. 96 (3): 372–6.  
  41. ^ Jiang Y, Langley B, Lubin FD, Renthal W, Wood MA, Yasui DH, Kumar A, Nestler EJ, Akbarian S, Beckel-Mitchener AC (November 2008). "Epigenetics in the nervous system". J. Neurosci. 28 (46): 11753–9.  
  42. ^ Philibert RA, Gunter TD, Beach SR, Brody GH, Madan A (July 2008). "MAO-A methylation is associated with nicotine and alcohol dependence in women". Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B (5): 565–70.  
  43. ^ Philibert RA, Wernett P, Plume J, Packer H, Brody GH, Beach SRH (July 2011). "Gene environment interactions with a novel variable Monoamine oxidase A transcriptional enhancer are associated with antisocial personality disorder". Biol. Psychol. 87 (3): 366–71.  
  44. ^ Wong CCY, Caspi A, Williams B, Craig IW, Houts R, Ambler A, Moffitt TE, Mill J (August 2010). "A longitudinal study of epigenetic variation in twins". Epigenetics 5 (6): 516–26.  
  45. ^ Barber N (2010-07-13). "Pity the poor murderer, his genes made him do it". The Human Beast: Why we do what we do. Psychology Today. Retrieved 2010-10-17. 
  46. ^ Hagerty BB (2010-07-01). "Can Your Genes Make You Murder?". News > Science > Inside The Criminal Brain. National Public Radio. Retrieved 2010-10-17. 
  47. ^ Pietrangeli P, Mondovi B (January 2004). "Amine oxidases and tumors". Neurotoxicology 25 (1-2): 317–24.  
  48. ^ Huang L, Frampton G, Rao A, Zhang KS, Chen W, Lai JM, Yin XY, Walker K, Culbreath B, Leyva-Illades D, Quinn M, McMillin M, Bradley M, Liang LJ, DeMorrow S (October 2012). "Monoamine oxidase A expression is suppressed in human cholangiocarcinoma via coordinated epigenetic and IL-6-driven events". Lab Invest. 92 (10): 1451–60.  
  49. ^ Wu JB, Shih JC (October 2011). "Valproic Acid Induces Monoamine Oxidase A via Akt/Forkhead Box O1 Activation". Mol Pharmacol. 80 (4): 714–723.  

Further reading

  • Warrior Gene' Predicts Aggressive Behavior After Provocation"'". Science News. Science Daily. 2009-01-23. 
  • McDermott R, Tingley D, Cowden J, Frazzetto G, Johnson DD (January 2009). "Monoamine oxidase A gene (MAOA) predicts behavioral aggression following provocation". Proc. Natl. Acad. Sci. U.S.A. 106 (7): 2118–23.  
  • Edmondson DE, Binda C, Mattevi A (2004). "The FAD binding sites of human monoamine oxidases A and B". Neurotoxicology 25 (1–2): 63–72.  
  • Craig IW (2007). "The importance of stress and genetic variation in human aggression". BioEssays 29 (3): 227–36.  
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 



Copyright © World Library Foundation. All rights reserved. eBooks from World eBook Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.