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Monoamine oxidase A, also known as MAOA, is an enzyme which in humans is encoded by the MAOA gene.[1][2] Monoamine oxidase A is an isozyme of monoamine oxidase. It preferentially deaminates norepinephrine (noradrenaline), epinephrine (adrenaline), serotonin, and dopamine (dopamine is equally deaminated by MAO-A and MAO-B). It is inhibited by clorgiline and befloxatone.

Function

This gene encodes monoamine oxidase A, an enzyme that degrades amine neurotransmitters, such as dopamine, norepinephrine, and serotonin. The protein localizes to the outer mitochondrial membrane. The gene is adjacent to a related gene (MAOB) on the opposite strand of chromosome X. Mutation in this gene results in monoamine oxidase deficiency, or Brunner syndrome.[3]

Clinical significance

An association between a rare 2 repeat of the VNTR region of the gene and an increase in the likelihood of committing serious crime or violence has been found.[4][5]

MAO-A levels in the brain as measured using positron emission tomography are elevated by an average of 34 percent in patients with major depressive disorder.[6] Genetic association studies examining the relationship between high-activity MAO-A variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females,[7] depressed suicide in males,[8] major depression and sleep disturbance in males[9] and major depressive disorder in both males and females.[10] Other studies failed to find a significant relationship between high-activity variants of the MAO-A gene and major depressive disorder.[11][12]

The version of the gene that a person carries may determine or at least significantly influence whether a traumatic childhood experience of violence leads to psychopathy,[13] but this finding is not universal; it was shown in Caucasian but not non-white Americans.[14]

In patients with major depressive disorder, those with MAO-A 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.[15]

Warrior gene

A version of the primate monoamine oxidase-A gene has been referred to as the warrior gene. 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).[16] The genotype associated with behavioural traits is shorter (30 bases) and may produce less MAO-A enzyme.[17] This gene variation is in a regulatory promoter region about 1000 bases from the start of the region that encodes the MAO-A enzyme. However, behaviour is dependent on both genes and the environment.[13]

This variant (or genotype) of monoamine oxidase-A was over-represented in a small sample of current Māori.[18] This supported earlier studies that there are different proportions of variants in different ethnic groups. This is the case for many genetic variants, with 33% White/Non-Hispanic, 61% Asian/Pacific Islanders having the shorter promoter variant of the MAO-A gene.[17][19] Due to the sensitive political nature of the findings, and the standard peer review process, the research has been heavily scrutinized. Several objections have been raised, such as the small sample size, and the extrapolation of non-Maori studies to the Maori population. In addition, ideological objections were raised, as well as concerns about announcing such findings in the early stages of research.[20][21][14][22]

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.[23][24]

Some MAO-A inhibitors

See also

References

  1. Hotamisligil GS, Breakefield XO (August 1991). "Human monoamine oxidase A gene determines levels of enzyme activity". Am. J. Hum. Genet. 49 (2): 383–92. PMC 1683299. PMID 1678250.
  2. 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. doi:10.1073/pnas.88.9.3637. PMC 51507. PMID 2023912.
  3. "Entrez Gene: MAOA monoamine oxidase A". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4128.
  4. Guo G, Roettger M, Shih JC (August 2008). "The integration of genetic propensities into social-control models of delinquency and violence among male youths" ([dead link]). American Sociological Review 73 (4): 543–568. doi:10.1177/000312240807300402. http://www.asanet.org/galleries/default-file/Aug08ASRFeature.pdf.
  5. 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. doi:10.1038/sj.ejhg.5201999. PMC 2922855. PMID 18212819.
  6. 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. doi:10.1001/archpsyc.63.11.1209. PMID 17088501.
  7. 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. doi:10.1002/1096-8628(20001204)96:6<801::AID-AJMG21>3.0.CO;2-4. PMID 11121185.
  8. Du L, Faludi G, Palkovits M, Sotonyi P, Bakish D, Hrdina PD (July 2002). "High activity-related allele of MAO-A gene associated with depressed suicide in males". Neuroreport 13 (9): 1195–8. doi:10.1097/00001756-200207020-00025. PMID 12151768.
  9. Du L, Bakish D, Ravindran A, Hrdina PD (September 2004). "MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males". Neuroreport 15 (13): 2097–101. doi:10.1097/00001756-200409150-00020. PMID 15486489.
  10. 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. doi:10.1038/sj.npp.1300785. PMID 15956990.
  11. 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, MAO-A, and DRD4 polymorphisms in mood disorders". Am. J. Med. Genet. 114 (4): 361–9. doi:10.1002/ajmg.10356. PMID 11992558.
  12. Huang SY, Lin MT, Lin WW, Huang CC, Shy MJ, Lu RB (December 2007). "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): 1–8. doi:10.1080/15622970701816506. PMID 19224413.
  13. 13.0 13.1 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. doi:10.1126/science.1072290. PMID 12161658. Lay summary – eurekalert.org (2002-08-01).
  14. 14.0 14.1 Crampton P, Parkin C (2007). "Warrior genes and risk-taking science". N. Z. Med. J. 120 (1250): U2439. PMID 17339895. http://www.nzma.org.nz/journal/120-1250/2439.
  15. 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. doi:10.1097/JCP.0b013e3181ac4aaf. PMID 19593178.
  16. Template:OMIM
  17. 17.0 17.1 Sabol SZ, Hu S, Hamer D (September 1998). "A functional polymorphism in the monoamine oxidase A gene promoter". Hum. Genet. 103 (3): 273–9. doi:10.1007/s004390050816. PMID 9799080.
  18. "Maori 'warrior' gene linked to aggression". National - NZ Herald News. The New Zealand Herald. http://www.nzherald.co.nz/section/story.cfm?c_id=1&ObjectID=10395334. Retrieved 2009-01-27.
  19. Lea R, Chambers G (2007). "Monoamine oxidase, addiction, and the "warrior" gene hypothesis". N. Z. Med. J. 120 (1250): U2441. PMID 17339897. http://www.nzma.org.nz/journal/120-1250/2441.
  20. "Maori 'warrior gene' claims appalling, says geneticist". News. NZ Herald News. http://www.nzherald.co.nz/category/story.cfm?c_id=204&objectid=10395491. Retrieved 2009-01-27.
  21. Whanau Tu, Whanau Ora (2007). "Hui Whakapiripiri Report". www.hrc.govt.nz. ISBN 978-0-908700-73-3. http://www.hrc.govt.nz/assets/pdfs/publications/Hui%20Report%2006%20FINAL.pdf. Retrieved 2009-01-27.
  22. "Scientist debunks 'warrior gene'". News. NZ Herald News. http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10596821. Retrieved 2009-09-11.
  23. 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. http://www.psychologytoday.com/blog/the-human-beast/201007/pity-the-poor-murderer-his-genes-made-him-do-it. Retrieved 2010-10-17.
  24. Hagerty BB (2010-07-01). "Can Your Genes Make You Murder?". News > Science > Inside The Criminal Brain. National Public Radio. http://www.npr.org/templates/story/story.php?storyId=128043329. Retrieved 2010-10-17.

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