Meta-analysis of the association between the monoamine oxidase-A gene and mood disorders

Objective To evaluate the controversial, putative associations between the three common polymorphisms [promoter variable number tandem repeat (uVNTR), T941G, (CA) repeat] of monoamine oxidase A (MAOA) and mood disorders (major depressive or bipolar disorders, BPD) by systematically meta-analyzing published case-control association studies. Methods We queried PubMed using the keywords ‘MAOA’, ‘association’ and ‘depression’ or ‘bipolar’. Nine studies on uVNTR, seven studies on T941G, and eight studies on CA met the inclusion criteria. The meta-analysis was performed by sex and ethnicity. Main results Our meta-analysis showed a significant association between uVNTR and MDD for the Asian group [odds ratio (OR) = 1.23 (1.02–1.47), P=0.03] and male Asian group [OR = 1.47 (1.06–2.05), P=0.02]. For the CA polymorphism, we found a significant association with BPD in the Caucasian group [OR = 1.28 (1.01–1.62), P=0.04] and female Caucasian group [OR = 1.36 (1.031–1.81), P=0.03]. For the CA polymorphism, we identified significant associations with BPD in all Caucasians for the overall alleles and for the specific alleles in a6 [OR = 1.35 (1.11–1.64), P=0.002] and in female Caucasians for the overall alleles and for the specific alleles in a2 [OR = 0.65 (0.48–0.90), P=0.009], a5 [OR = 1.44 (1.04–1.99), P=0.03], and a6 [OR = 1.41(1.12–1.78), P=0.004]. Conclusion Our meta-analysis suggests a significant association of the MAOA gene with major depressive disorder and BPD within specific groups, indicating that these three polymorphisms of the MAOA gene may be associated with mood disorders by sex and ethnicity. Moreover, our systematic meta-analysis has revealed that although MAOA may be a common candidate gene for mood disorders, different polymorphisms and alleles appear to play different roles in major depressive disorder and BPD.

[1]  R. Lu,et al.  Association of monoamine oxidase A (MAOA) polymorphisms and clinical subgroups of major depressive disorders in the Han Chinese population , 2009, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[2]  R. Lu,et al.  Neither single-marker nor haplotype analyses support an association between monoamine oxidase A gene and bipolar disorder , 2008, European Archives of Psychiatry and Clinical Neuroscience.

[3]  D. Levinson The Genetics of Depression: A Review , 2006, Biological Psychiatry.

[4]  S. Tsai,et al.  Association Study of a Monoamine Oxidase A Gene Promoter Polymorphism with Major Depressive Disorder and Antidepressant Response , 2005, Neuropsychopharmacology.

[5]  B. Gutiérrez,et al.  Association analysis between a functional polymorphism in the monoamine oxidase A gene promoter and severe mood disorders , 2004, Psychiatric genetics.

[6]  A. Ravindran,et al.  MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males , 2004, Neuroreport.

[7]  J. Mann,et al.  An Association between a Functional Polymorphism in the Monoamine Oxidase A Gene Promoter, Impulsive Traits and Early Abuse Experiences , 2004, Neuropsychopharmacology.

[8]  D. Rujescu,et al.  Association of a MAOA gene variant with generalized anxiety disorder, but not with panic disorder or major depression , 2003, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[9]  C. Cusin,et al.  Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders. , 2002, American journal of medical genetics.

[10]  N. Craddock,et al.  Association studies of bipolar disorder. , 2001, Bipolar disorders.

[11]  K. Lesch,et al.  Association analysis of the functional monoamine oxidase A gene promoter polymorphism in psychiatric disorders. , 2001, American journal of medical genetics.

[12]  T G Schulze,et al.  Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder. , 2000, American journal of medical genetics.

[13]  M. Leboyer,et al.  Association between bipolar disorder and monoamine oxidase A gene polymorphisms: results of a multicenter study. , 2000, The American journal of psychiatry.

[14]  Y. Qian,et al.  Association analysis between mood disorder and monoamine oxidase gene. , 2000, American journal of medical genetics.

[15]  G. Kirov,et al.  A functional polymorphism in the promoter of monoamine oxidase A gene and bipolar affective disorder. , 1999, The international journal of neuropsychopharmacology.

[16]  E. Paykel,et al.  Analysis of the monoamine oxidase A (MAOA) gene in bipolar affective disorder by association studies, meta-analyses, and sequencing of the promoter. , 1999, American journal of medical genetics.

[17]  S. Nanko,et al.  A functional polymorphism in the promoter region of monoamine oxidase-A gene and mood disorders , 1999, Molecular Psychiatry.

[18]  M. Nöthen,et al.  Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. , 1999, Human molecular genetics.

[19]  S. Nanko,et al.  The monoamine oxidase-a gene and major psychosis in japanese subjects , 1998, Biological Psychiatry.

[20]  D. Hamer,et al.  A functional polymorphism in the monoamine oxidase A gene promoter , 1998, Human Genetics.

[21]  S. Kanba,et al.  Monoamine oxidase genes polymorphisms and mood disorder. , 1997, American journal of medical genetics.

[22]  R. Todd,et al.  Genetic association between monoamine oxidase and manic-depressive illness: comparison of relative risk and haplotype relative risk data. , 1997, American journal of medical genetics.

[23]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[24]  E. Paykel,et al.  Genetic association between monoamine oxidase A microsatellite and RFLP alleles and bipolar affective disorder: analysis and meta-analysis. , 1996, Human molecular genetics.

[25]  R. Murray,et al.  Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder. , 1995, American journal of medical genetics.

[26]  N. Craddock,et al.  No evidence for allelic association between bipolar disorder and monoamine oxidase A gene polymorphisms. , 1995, American journal of medical genetics.

[27]  P. Gaspar,et al.  Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. , 1995, Science.

[28]  D. Curtis,et al.  Monte Carlo tests for associations between disease and alleles at highly polymorphic loci , 1995, Annals of human genetics.

[29]  M. Nelen,et al.  Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. , 1993, Science.

[30]  I. Craig,et al.  Characterization of a highly polymorphic region near the first exon of the human MAOA gene containing a GT dinucleotide and a novel VNTR motif. , 1992, Genomics.

[31]  X. Breakefield,et al.  Human monoamine oxidase A gene determines levels of enzyme activity. , 1991, American journal of human genetics.

[32]  I. Craig,et al.  Dinucleotide repeat polymorphism at the MAOA locus. , 1991, Nucleic acids research.

[33]  S. Gershon,et al.  Dopamine and depression , 2005, Journal of Neural Transmission / General Section JNT.

[34]  S. Nanko,et al.  Possible association between monoamine oxidase A gene and bipolar affective disorder. , 1995, American journal of human genetics.

[35]  T. Lai,et al.  Behavioral and Brain Functions Association Analysis of Monoamine Oxidase a Gene and Bipolar Affective Disorder in Han Chinese , 2022 .