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==Warrior gene==
==Warrior gene==
A version of the primate [[monoamine oxidase]]-A gene has been popularly 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]]).<ref name="maoa">{{OMIM|309850|MONOAMINE OXIDASE A; MAOA.}}</ref> The allele associated with behavioural traits is shorter (30 [[base pair|bases]]) and may produce less MAO-A enzyme.<ref name="pmid9799080">{{cite journal | author = Sabol SZ, Hu S, Hamer D | title = A functional polymorphism in the monoamine oxidase A gene promoter | journal = Hum. Genet. | volume = 103 | issue = 3 | pages = 273–9 | year = 1998 | month = September | pmid = 9799080 | doi = 10.1007/s004390050816 }}</ref> This gene variation is in a regulatory [[promoter (biology)|promoter]] region about 1000 [[bases]] from the [[start codon|start]] of the region that [[translation (genetics)|encodes]] the MAO-A enzyme. However, behaviour is dependent on both genes and the environment.<ref name= "pmid12161658">{{cite journal |author=Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R | title = Role of genotype in the cycle of violence in maltreated children | journal = Science | volume = 297 | issue = 5582 | pages = 851–4 | year = 2002 | month = August | pmid = 12161658 | doi = 10.1126/science.1072290 | laysummary = http://www.eurekalert.org/pub_releases/2002-08/uow-gmp072602.php | laysource = eurekalert.org | laydate = 2002-08-01 }}</ref>
A version of the primate [[monoamine oxidase]]-A gene has been popularly 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]]).<ref name="maoa">{{OMIM|309850|MONOAMINE OXIDASE A; MAOA.}}</ref> The allele associated with behavioural traits is shorter (30 [[base pair|bases]]) and may produce less MAO-A enzyme.<ref name="pmid9799080">{{cite journal | author = Sabol SZ, Hu S, Hamer D | title = A functional polymorphism in the monoamine oxidase A gene promoter | journal = Hum. Genet. | volume = 103 | issue = 3 | pages = 273–9 | year = 1998 | month = September | pmid = 9799080 | doi = 10.1007/s004390050816 }}</ref> This gene variation is in a regulatory [[promoter (biology)|promoter]] region about 1000 [[bases]] from the [[start codon|start]] of the region that [[translation (genetics)|encodes]] the MAO-A enzyme.
A 2002 study found a connection of this version of the gene with [[ancisocial personality disorder]].
This study is known as the ''Dunedin Multidisciplinary Health and Development Study'', based on a sample of 1047 probands born in [[Dunedin, New Zealand]]. The authors divided participants into two bins of "low" and "high" MAO-A activity. They then diagnosed participants according to four criteria of antisocial behaviour. In all four types of antisocial behaviour, low MAO-A activity was found to be a significant risk factor.
85% of men with low MAO-A activity exhibited a type of antisocial behaviour as defined in the study.
<ref name= "pmid12161658">{{cite journal |author=Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R | title = Role of genotype in the cycle of violence in maltreated children | journal = Science | volume = 297 | issue = 5582 | pages = 851–4 | year = 2002 | month = August | pmid = 12161658 | doi = 10.1126/science.1072290 | laysummary = http://www.eurekalert.org/pub_releases/2002-08/uow-gmp072602.php | laysource = eurekalert.org | laydate = 2002-08-01 }}</ref>
Follow-up studies published between 2004 and 2006 in part confirmed the conclusions of the Dunedin study, and in part found no independent confirmation. Frazzetto et al. (2007) found that low MAO-A activity in combination with abuse experienced during childhood results in an increased risk of aggressive behaviour as an adult.<ref>{{cite journal |author=Frazzetto G, Di Lorenzo G, Carola V, ''et al.'' |title=Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype |journal=PLoS ONE |volume=2 |issue=5 |pages=e486 |year=2007 |pmid=17534436 |pmc=1872046 |doi=10.1371/journal.pone.0000486 |url=}}</ref>


The frequency distribution of variants of the MAO-A gene differs between ethnic groups<ref name="pmid9799080"/><ref name="pmid17339897">{{cite journal | author = Lea R, Chambers G | title = Monoamine oxidase, addiction, and the "warrior" gene hypothesis | journal = N. Z. Med. J. | volume = 120 | issue = 1250 | pages = U2441 | year = 2007 | pmid = 17339897 | doi = | url = http://journal.nzma.org.nz/journal/120-1250/2441/ }}</ref>&mdash;as is the case for many genotypes. Due to the sensitive political nature of the findings, and the standard peer review process, the research has been heavily scrutinised.
The frequency distribution of variants of the MAO-A gene differs between ethnic groups<ref name="pmid9799080"/><ref name="pmid17339897">{{cite journal | author = Lea R, Chambers G | title = Monoamine oxidase, addiction, and the "warrior" gene hypothesis | journal = N. Z. Med. J. | volume = 120 | issue = 1250 | pages = U2441 | year = 2007 | pmid = 17339897 | doi = | url = http://journal.nzma.org.nz/journal/120-1250/2441/ }}</ref>&mdash;as is the case for many genotypes. Due to the sensitive political nature of the findings, and the standard peer review process, the research has been heavily scrutinised.

Revision as of 15:26, 26 February 2012

Template:PBB Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAO-A 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

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 (MAO-B) on the opposite strand of chromosome X. Mutation in this gene results in monoamine oxidase deficiency, or Brunner syndrome.[3]

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

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.[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]

A dysfunctional MAO-A gene has been correlated with increased aggression levels in mice,[16][17] and in some studies, has been correlated with heightened levels of aggression in humans.[18] The correlation between a dysfunctional MAO-A gene and heightened levels of aggression in humans remains controversial.[19] However, there is research in both humans and mice to support that a spontaneous point nonsense mutation in the eighth exon of the MAO-A gene is responsible for impulsive aggressiveness due to a complete MAO-A deficiency.[16][18]

Warrior gene

A version of the primate monoamine oxidase-A gene has been popularly 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).[20] The allele associated with behavioural traits is shorter (30 bases) and may produce less MAO-A enzyme.[21] This gene variation is in a regulatory promoter region about 1000 bases from the start of the region that encodes the MAO-A enzyme.

A 2002 study found a connection of this version of the gene with ancisocial personality disorder. This study is known as the Dunedin Multidisciplinary Health and Development Study, based on a sample of 1047 probands born in Dunedin, New Zealand. The authors divided participants into two bins of "low" and "high" MAO-A activity. They then diagnosed participants according to four criteria of antisocial behaviour. In all four types of antisocial behaviour, low MAO-A activity was found to be a significant risk factor. 85% of men with low MAO-A activity exhibited a type of antisocial behaviour as defined in the study. [13] Follow-up studies published between 2004 and 2006 in part confirmed the conclusions of the Dunedin study, and in part found no independent confirmation. Frazzetto et al. (2007) found that low MAO-A activity in combination with abuse experienced during childhood results in an increased risk of aggressive behaviour as an adult.[22]

The frequency distribution of variants of the MAO-A gene differs between ethnic groups[21][23]—as is the case for many genotypes. Due to the sensitive political nature of the findings, and the standard peer review process, the research has been heavily scrutinised. 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.[14][24][25][26]

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 jail [27][28]

Some MAO-A inhibitors

References

  1. ^ Hotamisligil GS, Breakefield XO (1991). "Human monoamine oxidase A gene determines levels of enzyme activity". Am. J. Hum. Genet. 49 (2): 383–92. PMC 1683299. PMID 1678250. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ Grimsby J, Chen K, Wang LJ, Lan NC, Shih JC (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ "Entrez Gene: MAOA monoamine oxidase A".
  4. ^ a b Guo G, Ou XM, Roettger M, Shih JC (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Guo G, Roettger M, Shih JC (2008). "The integration of genetic propensities into social-control models of delinquency and violence among male youths" (PDF). American Sociological Review. 73 (4): 543–568. doi:10.1177/000312240807300402. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) [dead link]
  6. ^ Meyer JH, Ginovart N, Boovariwala A, Sagrati S, Hussey D, Garcia A, Young T, Praschak-Rieder N, Wilson AA, Houle S (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  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 (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ Du L, Faludi G, Palkovits M, Sotonyi P, Bakish D, Hrdina PD (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Du L, Bakish D, Ravindran A, Hrdina PD (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  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 (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ 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. doi:10.1080/15622970701816506. PMID 19224413.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ a b Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002). "Role of genotype in the cycle of violence in maltreated children". Science. 297 (5582): 851–4. doi:10.1126/science.1072290. PMID 12161658. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ a b Crampton P, Parkin C (2007). "Warrior genes and risk-taking science". N. Z. Med. J. 120 (1250): U2439. PMID 17339895.
  15. ^ Leuchter AF, McCracken JT, Hunter AM, Cook IA, Alpert JE (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ a b Scott AL, Bortolato M, Chen K, Shih JC (2008). "Novel monoamine oxidase A knock out mice with human-like spontaneous mutation". Neuroreport. 19 (7): 739–43. doi:10.1097/WNR.0b013e3282fd6e88. PMID 18418249. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ 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. doi:10.1002/ab.20161. PMID 17441000.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ^ a b Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (1993). "Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A". Science. 262 (5133): 578–80. doi:10.1126/science.8211186. PMID 8211186. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  19. ^ Hebebrand J, Klug B (1995). "Specification of the phenotype required for men with monoamine oxidase type A deficiency". Hum. Genet. 96 (3): 372–6. doi:10.1007/BF00210430. PMID 7649563. {{cite journal}}: Unknown parameter |month= ignored (help)
  20. ^ Online Mendelian Inheritance in Man (OMIM): MONOAMINE OXIDASE A; MAOA. - 309850
  21. ^ a b Sabol SZ, Hu S, Hamer D (1998). "A functional polymorphism in the monoamine oxidase A gene promoter". Hum. Genet. 103 (3): 273–9. doi:10.1007/s004390050816. PMID 9799080. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ Frazzetto G, Di Lorenzo G, Carola V; et al. (2007). "Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype". PLoS ONE. 2 (5): e486. doi:10.1371/journal.pone.0000486. PMC 1872046. PMID 17534436. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  23. ^ Lea R, Chambers G (2007). "Monoamine oxidase, addiction, and the "warrior" gene hypothesis". N. Z. Med. J. 120 (1250): U2441. PMID 17339897.
  24. ^ "Maori 'warrior gene' claims appalling, says geneticist". News. NZ Herald News. Retrieved 2009-01-27.
  25. ^ Whanau Tu, Whanau Ora (2007). Hui Whakapiripiri Report (PDF). www.hrc.govt.nz. ISBN 978-0-908700-73-3. Retrieved 2009-01-27. {{cite book}}: Check |isbn= value: checksum (help)
  26. ^ "Scientist debunks 'warrior gene'". News. NZ Herald News. Retrieved 2009-09-11.
  27. ^ 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.
  28. ^ Hagerty BB (2010-07-01). "Can Your Genes Make You Murder?". News > Science > Inside The Criminal Brain. National Public Radio. Retrieved 2010-10-17.

Further reading

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