Abstract OBJECTIVE: To investigate whether the genetic polymorphism, upstream variable number of tandem repeats (uVNTR), in the monoamine oxidase A (MAOA) gene, is associated with major depressive disorder (MDD) in adolescents and to test whether there is gene-environment interaction between MAOA-uVNTR polymorphism and stressful life events (SLEs). METHODS: A total of 394 Chinese Han subjects, including 187 adolescent patients with MDD and 207 normal students as a control group, were included in the study. Genotyping was performed by SNaP-shot assay. SLEs in the previous 12 months were evaluated. The groups were compared in terms of the frequency distributions of MAOA-uVNTR genotypes and alleles using statistical software. The binary logistic regression model of gene-environment interaction was established to analyze the association of the gene-environment interaction between MAOA-u VNTR genotypes and SLEs with adolescent MDD. RESULTS: The distribution profiles of MAOA-u VNTR genotypes and alleles were not related to the onset of MDD, severity of depression, comorbid anxiety and suicidal ideation/behavior/attempt in adolescents. The gene-environment interaction between MAOA-u VNTR genotypes and SLEs was not associated with MDD in male or female adolescents. CONCLUSIONS: It is not proven that MAOA-u VNTR polymorphism is associated with adolescent MDD. There is also no gene-environment interaction between MAOA-u VNTR polymorphism and SLEs that is associated with adolescent MDD.
MA Jing,YU Shun-Ying,LIANG Shan et al. Association between MAOA-u VNTR polymorphism and its interaction with stressful life events and major depressive disorder in adolescents[J]. CJCP, 2013, 15(7): 563-568.
MA Jing,YU Shun-Ying,LIANG Shan et al. Association between MAOA-u VNTR polymorphism and its interaction with stressful life events and major depressive disorder in adolescents[J]. CJCP, 2013, 15(7): 563-568.
[1]Lung FW, Tzeng DS, Huang MF, Lee MB.Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder[J]. BMC Med Genet, 2011, 12: 74.
[2]Zhang JX, Chen YB, Zhang KR, Xu Q, Shen Y. Relationship of genetic variability and depressive symptoms to adverse events after coronary artery bypass graft surgery[J].Psychosom Med, 2008, 70(9): 953-959.
[3]Priess-Groben HA, Hyde JS. 5-HTTLPR X stress in adolescent depression: moderation by MAOA and gender[J]. J Abnorm Child Psychol, 2013, 41(2):281-294.
[5]Brummett BH, Krystal AD, Siegler IC, Kuhn C, Surwit RS, Züchner S, et al. Associations of a regulatory polymorphism of monoamine oxidase-A gene promoter (MAOA-uVNTR) with symptoms of depression and sleep quality[J]. Psychosom Med, 2007, 69(5): 396-401.
[6]Meyer-Lindenberg A, Buckholtz JW, Kolachana B, R Hariri A, Pezawas L, Blasi G, et al. Neural mechanisms of genetic risk for impulsivity and violence in humans[J]. Proc Natl Acad Sci, 2006, 103(16): 6269-6274.
[7]Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW, et al. MAOA, maltreatment, and gene-environment interaction predicting children′s mental health: New evidence and a meta-analysis[J]. Mol Psychiatry, 2006, 11: 903-913.
[8]Sabol SZ, Hu S, Hamer D. A functional polymorphism in the monoamine oxidase A gene promoter[J]. Hum Genet, 1998, 103(3): 273-279.
[9]Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams JD, et al. Increased stress response and beta-phenylethylamine in MAOB-deficient mice[J]. Nat Genet, 1997, 17(2): 206-210.
[10]Shih JC, Chen K, Riddl MJ. Role of MAO A and B inneurotransmitter metabolism and behavior[J]. Pol J Pharmacol, 1999, 51(1): 25-29.
[11]Kersting A, Kroker K, Horstmann J, Baune BT, Hohoff C, Mortensen LS, et al. Association of MAO-A variant with complicated grief in major depression[J]. Neuropsychobiol, 2007, 56(4): 191-196.
[12]Rende R, Waldman I. Behavioral and molecular genetics and developmental psychopathology[M]// Cicchetti D, Cohen D, ed. Developmental Psychopathology. 2nd ed. New York: Wiley, 2006: 427-464
[13]Nakamura K, Sekine Y, Takei N, Iwata Y, Suzuki K, Anitha A, et al. An association study of monoamine oxidase A (MAOA) gene polymorphism in methamphetamine psychosis[J]. Neurosci Lett, 2009, 455(2): 120-123.
[14]Dannlowski U, Ohrmann P, Konrad C, Domschke K, Bauer J, Kugel H, et al. Reduced amyg-dala-prefrontal coupling in major depression: association with MAOA genotype and illness severity[J]. Int J Neuropsychopharmacol, 2009, 12(1): 11-22.
[15]Buckholtz JW, Meyer-Lindenberg A. MAOA and the neurogenetic architecture of human aggression[J]. Trends Neurosci, 2008, 31(3): 120-129.
[16]Jollant F, Buresi C, Guillaume S, Jaussent I, Bellivier F, Leboyer M, et al. The influence of four serotoninrelated genes on decision-making in suicide attempters[J]. Am J Med Genet B Neuro-psychiatr Genet, 2007, 144B(5): 615-624.
[17]Das M, Bhowmik AD, Sinha S, Chattopadhyay A, Chaudhuri K, Singh M, et al. MAOA promoter polymorphism and attention deficit hyperactivity disorder (ADHD) in indian children[J]. Am J Med Genet B Neuropsychiatr Genet, 2006, 141B(6): 637-642.
[18]Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF. A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity[J]. Psychiatry Res, 2000, 95(1): 9-23.
[19]Manuck SB, Flory JD, Muldoon MF, Ferrell RE. Central nervous system serotonergic responsivity and aggressive disposition in men[J]. Physiol Behav, 2002, 77(4-5): 705-709.
[20]Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, et al. Role of genotype in the cycle of violence in maltreated children[J]. Science, 2002, 297(5582): 851-854.
[21]Eley TC, Tahir E, Angleitner A, Harriss K, McClay J, Plomin R, et al. Association analysis of MAOA and COMT with neuroticism assessed by peers[J]. Am J Med Genet B Neuropsychiatr Genet, 2003, 120B(1): 90-96.
[22]Fan M, Liu B, Jiang T, Jiang X, Zhao H, Zhang J. Meta-analysis of the association between the monoamine oxidase-A gene and mood disorders[J]. Psychiatr Genet, 2010, 20(1): 1-7.
[23]Christiansen L, Tan Q, Iachina M, Bathum L, Kruse TA, McGue M, et al. Candidate gene poly-morphisms in the serotonergic pathway: influence on depression symptomatology in an elderly population[J]. Biol Psychiatry, 2007, 61(2): 223-230.
[24]De Luca V, Tharmalingam S, Muller DJ, Wong G, de Bartolomeis A, Kennedy JL. Gene-gene interaction between MAOA and COMT in suicidal behavior: analysis in schizophrenia[J]. Brain Res, 2006, 1097(1): 26-30.
[25]Doornbos B, Dijck-Brouwer DA, Kema IP, Tanke MA, van Goor SA, Muskiet FA, et al. The development of peripartum depressive symptoms is associated with gene polymorphisms of MAOA, 5-HTT and COMT[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2009, 33(7): 1250-1254.
[27]Tzeng DS, Chien CC, Lung FW, Yang CY. MAOA gene polymorphisms and response to mirtazapine in major depression[J]. Hum Psychopharmacol, 2009, 24(4): 293-300.
[28]Syagailo YV, Stober G, Grassle M, Reimer E, Knapp M, Jungkunz G, et al. Association analysis of the functional monoamine oxidase A gene promoter polymorphism in psychiatric disorders[J]. Am J Med Genet, 2001, 105(2): 168-171.
[29]Phillips-Bute B, Mathew JP, Blumenthal JA, Morris RW, Podgoreanu MV, Smith M, et al. Relationship of genetic variability and depressive symptoms to adverse events after coronary artery bypass graft surgery[J]. Psychosom Med, 2008, 70(9): 953-959.
[30]Yoshida K, Naito S, Takahashi H, Sato K, Ito K, Kamata M, et al. Monoamine oxidase: A gene polymorphism, tryptophan hydroxylase gene polymophism and antidepressant response to flu-voxamine in Japanese patients with major depressive disorder[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2002, 26(7-8): 1279-1283.
[31]Bernet W, Vnencak-Jones CL, Farahany N, Montgomery SA. Bad nature, bad nurture, and tes-timony regarding MAOA and SLC6A4 genotyping at murder trials[J]. J Forensic Sci, 2007, 52(6): 1362-1371.
[32]Eley TC, Sugden K, Corsico A, Gregory AM, Sham P, McGuffin P, et al. Gene-environment interaction analysis of serotonin system markers with adolescent depression[J]. Mol Psychiatry, 2004, 9(10): 908-915.
[33]Beach SR, Brody GH, Gunter TD, Packer H, Wernett P, Philibert RA. Child maltreatment moderates the association of MAOA with symptoms of depression and antisocial personality disorder[J]. J Fam Psychol, 2010, 24(1): 12-20.
[34]Cicchetti D, Rogosch FA, Sturge-Apple ML. Interactions of child maltreatment and serotonin transporter and monoamine oxidase A polymorphisms: depressive symptomatology among adolescents from low socioeconomic status backgrounds[J]. Dev Psychopathol, 2007, 19(4): 1161-1180.
[35]Kinnally EL, Huang YY, Haverly R, Burke AK, Galfalvy H, Brent DP, et al. Parental care moderates the influence of MAOA-uVNTR genotype and childhood stressors on trait impulsivity and aggression in adult women[J]. Psychiatr Genet, 2009, 19(3): 126-133.