Monoamine Oxidase A Gene Polymorphism Research Articles

Relationship between the monoamine oxidase gene overactivity and the other pathophysiological and behavioral parameters implicated in memory deficiency in albino Winstar rats as Alzheimer’s disease model

The current study aimed to assess the pathophysiology mechanisms that mediate the effect on albin winstar rats' memory induced by the co -administration of fluoride and aluminum sulfate, as a model of Alzheimer's disease. This was done by assessing monoamine oxidase-A (MAO-A) activity, antioxidant activity, H2O2 and amyloid-β concentration in the hippocampus, embedded deep into the brain's temporal lobe, and level of cytokines in serum. The polymerase chain reaction approach was used to genotyping MAO-A, followed by single -stranded conformational polymorphism (SSCP) coupled with sequencing technique. The experimental animals were divided into two groups: control and treated groups. The uptake of heavy metals led to significantly increased MAO-A activity, amyloid -β deposition, H2O2 and cytokines levels in the treated group. However, the finding showed a significant decrease in antioxidant activity in the treated group. The results indicated that metals caused memory and learning impairments. PCR -SSCP genotyping showed many SNPs and haplotypes of the MAO-A exon 2 region, which showed the MAO-A gene polymorphism changes associated with Alzheimer's disease. The overall results indicated a role of metals to induce oxidative stress stimulating pathophysiological hallmarks in the hippocampus due to an increase in the influx of monoamine oxidase expression, which has been implicated in impaired memory, this study focused on the genetic variation of the exon 2 in monoamine oxidase-A gene and its relationship to Alzheimer's disease with the presence of several single nucleotide polymorphisms that may be related to Alzheimer's disease model in rats.

Roles of Hostility and Depression in the Association between the MAOA Gene Polymorphism and Internet Gaming Disorder.

The metabolism of bioamine in the central nervous system contributes to the development of addiction. We examined the roles of hostility and depression in the association between internet gaming disorder (IGD) and monoamine oxidase-A (MAOA) EcoRV polymorphism (rs1137070). A total of 69 adults with IGD and 138 without IGD were recruited through diagnostic interviewing. We evaluated participants for rs1137070, depression, and hostility. The participants with the TT genotype of rs1137070 had a higher odds ratio of 2.52 (1.37–4.64) for IGD compared with the C carriers. Expressive hostility behavior and hostility cognition mediated the association between rs1137070 and IGD. Indicating lower MAOA activity, the TT genotype predicted IGD and higher expressive hostility behavior and hostility cognition. Expressive hostility behavior and hostility cognition may underline the association between rs1137070 and IGD. Assessment of and intervention for hostility behavior and cognition should be provided to attenuate the risk of IGD, particularly in those with the TT genotype. Further brain imaging or neurobiological studies are required to elucidate the possible mechanism underlying the association between MAOA activity and IGD.

Association Analysis of Maoa and Slc6a4 Gene Variation in South East European War Related Posttraumatic Stress Disorder.

The aim of this study is to investigate the association of gene variations of the monoamine oxidase A (MAOA) and the serotonin transporter solute carrier family 6 member 4 (SLC6A4) gene with posttraumatic stress disorder (PTSD) severity and coping strategies in patients with war related PTSD. The study included 747 individuals who had experienced war trauma in the South Eastern Europe conflicts between 1991 and 1999. Genotyping of the MAOA VNTR and SLC6A4 tandem repeat polymorphism in combination with rs25531 was done in 719 participants: 232 females and 487 males. Among them, 369 have had current or lifetime PTSD and 350 have had no PTSD symptoms. For psychometric approach we used the Clinician Administrated PTSD Scale (CAPS), the Brief Symptom Inventory (BSI), the adapted Hoffman-Lazarus Coping scale and a basic socio-demographic data questionnaire. There were no significant intergroup (PTSD versus non PTSD) differences in the genotype distribution of MAOA and SLC6A4 gene polymorphisms. The primary finding of our study was that the MAOA short allele (MAOA-S) was nominally significantly associated with the severity of PTSD symptoms in the total subgroup of participants with lifetime PTSD; males for symptoms of hyperarrousal and females with symptoms of re-experience and hyperarousal. In our research the male subsample with current PTSD and MAOA-S genotype had nominally significantly higher scores for some positive coping strategies compared to those carrying the long allele genotype (MAOA-L). There was no significant association between the severity of PTSD symptoms, BSI phenotype, coping scores and the SLC6A4 genotype. The present results support the notion that MAOA VNTR gene variation modulates development and recovery of posttraumatic stress disorder in a war traumatised population, but did not support a connection between SLC6A4 gene variations and war related PTSD.

Associations of serotonin transporter gene promoter polymorphisms and monoamine oxidase A gene polymorphisms with oppositional defiant disorder in a Chinese Han population

BackgroundOppositional defiant disorder (ODD) is a behavioral disorder that mainly refers to a recurrent pattern of disobedient, defiant, negativistic and hostile behaviors toward authority figures. Previous studies have showed associations of serotonin transporter (5-HTT) and monoamine oxidase A (MAOA) with behavioral and psychiatric disorders. The purposes of this study were to investigate the potential association of 5-HTT gene promoter polymorphism (5-HTTLPR) and MAOA gene polymorphism with susceptibility to ODD in a Han Chinese school population.MethodsThe 5-HTTLPR gene polymorphism and the MAOA gene polymorphism were genotyped in a case–control study of 257 Han Chinese children (123 ODD and 134 healthy controls).ResultsThere was significant difference in the allele distribution of 5-HTTLPR (χ2 = 7.849, P = 0.005) between the ODD and control groups. Further, there were significant differences in genotype (χ2 = 5.168, P = 0.023) and allele distributions (χ2 = 10.336, P = 0.001) of the MAOA gene polymorphism that is variable-number tandem repeat (MAOA-uVNTR) between two groups. Moreover, there were significant differences in genotype (χ2 = 4.624, P = 0.032) and allele distributions (χ2 = 9.248, P = 0.002) of MAOA-uVNTR only in the male ODD and healthy groups.ConclusionsOur results suggest that 5-HTTLPR and MAOA-uVNTR gene variants may contribute to susceptibility to ODD. Further, MAOA-uVNTR gene polymorphism may play a role in susceptibility to ODD only in male children.

Association study of the polymorphism of MAOA gene with panic disorder

Objective To explore the association between monoamine oxidase A (MAOA) variable number tandem repeat (VNTR) polymorphism and panic disorder, and then to compare panic disorder(PD) severity patient with different MAOA VNTR genotypes. Methods The structured clinical interview for the diagnostic and statistical manual of mental disorders fourth edition (DSM-IV) Axis I Disorders (SCID-1) was administered by a trained clinical psychiatrist, 135 patients with PD and 195 healthy controls were recruited.MAOA-VNTR polymorphism were measured by fluorescent tags amplification product length polymorphism technology, Chi-square test was used to compare the distribution difference between each genotype and the allele frequency distribution. Results ①Whether male or female, there was no statistically significant difference between case group and healthy control group in the genotype and allele frequencies of MAOA-VNTR polymorphism (χ2=1.574, 1.894, 3.588; all P 0.05). ③However, there was significant difference between genotypes and panic disorder severity in the female with panic disorder((13.15±3.47), (16.57±4.34), (15.27±4.91); F=4.222, P<0.05). MAOA VNTR-L/L carriers experienced more serious panic (16.57±4.34) than the patient with MAOA VNTR-H/H (13.15±3.47)(P<0.01) by LSD multiple test. Conclusion No association between MAOA-VNTR polymorphism and panic disorder is found in Chinese Han population, but low activity homozygous genotype may be related to the severity of panic disorder in female patient with panic disorder. Key words: Panic disorder; Monoamine oxidase A gene; Polymorphism

Interactions between MAOA gene polymorphism and maternal parenting in predicting externalizing and internalizing problems and social competence among Chinese children: Testing the genetic vulnerability and differential susceptibility models

AbstractThe present study aimed to test whether monoamine oxidase A (MAOA) gene polymorphism was a marker of the genetic vulnerability model or the differential susceptibility model by investigating the interaction of MAOA gene polymorphism with maternal parenting on externalizing and internalizing problems and social competence among Chinese children. Participants were 290 children and their parents in China. MAOA genotypes were ascertained by polymerase chain reaction amplification. Mothers reported their parenting stress and engagement in parent–child activities when the child was 6 months old. Children's behavioral problems and social competence were rated by mothers and fathers at 48 months old. The results showed that MAOA genotypes interacted with maternal parenting stress in predicting boys' internalizing problems. Also, MAOA genotypes interacted with maternal engagement in parent–child activities in predicting boys' social competence. The analyses of regions of significance and the proportion of interaction index indicated that boys with the low‐activity genotype were at risk for (a) high internalizing problems under high maternal parenting stress and (b) low social competence if mothers displayed a low level of maternal engagement. No significant interaction effects were found among girls. The results suggested that the MAOA gene might be a marker of the genetic vulnerability model among Chinese boys.Highlights We evaluated whether MAOA gene was a marker of the genetic vulnerability model or the differential susceptibility model by investigating the interaction of MAOA gene polymorphism with maternal parenting on behavioral problems and social competence among 4‐year‐old Chinese children. The results of regions of significance and the proportion of interaction index indicated that boys with the low‐activity genotype were at risk of high internalizing problems or low social competence with high maternal parenting stress or low engagement. No significant interaction effects were found among girls. The results indicated that MAOA gene might be a marker of the genetic vulnerability model rather than the differential susceptibility model.

Investigation of the relationship between monoamine oxidase A enzyme gene polymorphism and the development of conduct disorder in sexually abused cases

Objective: Our aim in this study is to investigate whether there is a relationship between monoamine oxidase A (MAO-A) gene polymorphisms in sexually abused cases with or without conduct disorder (CD). Methods: Cases were recruited from sexually abused girls (n=52) aged between 13 and 18 who admitted to child psychiatry outpatient clinic. Psychiatric diagnoses were performed by using Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version according to DSM-IV by child psychiatrist. Blood samples were taken from participants and single nucleotide polymorphisms (SNPs) (rs1799835, rs1137070 and rs2072743) were analyzed to detect MAO-A gene polymorphism at Department of Medical Genetics. Results: There was no statistically significant difference between groups with or without CD in terms of rs1799835, rs1137070 and rs2072743 SNPs. Besides, no difference was detected between alleles, genotype frequencies of SNPs and three determined haplotypes in groups with (n=10) or without (n=42) CD in the whole sample. Conclusion: MAO-A gene polymorphism role in the development of CD did not differ between the groups with or without CD in sexually abused cases. It is known that there are a number of factors that play a role of development of CD rather than a diversification of a single gene.

Factors associated with post‐stroke anger proneness in ischaemic stroke patients

Factors related to post- stroke anger proneness (PSAP) are poorly studied. The aim of the present study was to determine the frequency of, and the factors related to, PSAP in the acute stage of stroke. Serotonin transporter protein genes and monoamine oxidase A (MAO-A) gene polymorphisms were also examined. A total of 508 patients with acute IS were screened for PSAP at admission after stroke, using the modified Spielberger Trait Anger Scale. Blood samples were collected from each participant for DNA extraction and genotyping. The promoter of serotonin transporter protein (5-HTTLPR), the variable number of tandem repeat polymorphisms within intron 2 (VNTR STin2), and the 30-bp functional VNTR polymorphism in the promoter region of the MAO-A gene (MAOA-uVNTR) were genotyped. Post- stroke anger proneness was present in 15.1% of patients at admission. The factors related to PSAP were diabetes mellitus (P < 0.05), previous stroke (P < 0.01), motor and sensory dysfunction (P < 0.01), National Institutes of Health Stroke Scale (NIHSS) at admission (P < 0.01), and MAO-A gene polymorphism (P < 0.05). Multiple logistic regression analyses showed that previous stroke (95% CI: 1.33-4.25, P < 0.01), NIHSS at admission (95% CI: 1.09-1.26, P < 0.01), and low MAO-A activity (95% CI: 1.19-3.47, P = 0.01) were the factors related to PSAP. Our results show that PSAP is relatively prevalent and that previous stroke, neurological dysfunction and the MAO-A gene are involved in the development of PSAP.

Association of MAOA and COMT gene polymorphisms with palatable food intake in children

Several studies have implicated dopamine (DA) in appetite regulation. The enzymes catechol-o-methyltransferase (COMT) and monoamine oxidase A (MAOA) control DA availability and their genes have well-characterized functional variants. In this study, we examined three polymorphisms in these genes, T941G and MAOAu-VNTR in the MAOA gene and Val158Met in the COMT gene, to investigate how heritable variations in enzymes that determine DA levels might influence food intake and nutritional status. This investigation was a cross-sectional examination of 354 Brazilian children of three to four years old. Polymorphisms were analyzed by PCR-based methods. Means of dietary and anthropometric data were compared among genotypes by one-way analyses of variance or Kruskal Wallis tests. The MAOAu-VNTR and COMT Val158Met polymorphisms were associated with the amount of palatable food intake in boys. Presence of the MAOAu-VNTR⁎long allele was associated with higher intake of lipid-dense foods (LDF) when compared with the ⁎short allele (P=.009); the amount of sugar-dense foods (SDF) intake was also higher in males carriers of the MAOAu-VNTR⁎long allele than in carriers of the ⁎short allele (P=.034). In the girls' sample, MAOAu-VNTR polymorphism was not associated with food intake and nutritional status. Carriers of the COMT Val158Met⁎Val allele presented higher intake of LDF when compared with Met/Met homozygotes (P=.008). This study provides the first indication that genetic variants of enzymes that control DA availability might be involved in determination of the amount of palatable food intake in children.

The interleukin-6, serotonin transporter, and monoamine oxidase A genes and endurance performance during the South African Ironman Triathlon

Previous studies have identified an association of genetic variants believed to alter physiological and biochemical processes locally within the skeletal muscle and therefore performance in the Ironman triathlon. There is growing evidence that the serotonergic system and circulating interleukin (IL)-6 levels are also involved in mediating endurance capacity. Investigators have demonstrated that recombinant human IL-6 administration and serotonergic neurotransmission manipulation, with 5-hydroxytryptamine transporter (5-HTT) and monoamine oxidase A (MAO-A) inhibitors, prior to exercise, can alter running performance, consistent with a central governor hypothesis. The aim of this study was to investigate possible associations of functional polymorphisms within the IL-6, 5-HTT, and MAO-A genes with endurance performance of Ironman triathletes. Four hundred sixty-eight male Caucasian triathletes who completed the 2000 and (or) 2001 South African Ironman Triathlon and 200 healthy Caucasian male controls were genotyped for the -174 IL-6 G/C, 5-HTT 40 base pair (bp) insertion-deletion and 30 bp variable number of tandem repeats (VNTR) MAO-A gene polymorphisms. There were no significant differences in the relative genotype distributions within the IL-6 (p = 0.636), 5-HTT (p = 0.659), and MOA-A (p = 0.227) polymorphisms when the fastest-fnishing, middle-finishing, and slowest-finishing triathletes, as well as the control groups, were compared. There were no direct associations between the IL-6 -174 G/C, 5-HTT 44 bp insertion-deletion, and MAO-A 30 bp VNTR gene polymorphisms and endurance performance in the 2000 and (or) 2001 South African Ironman Triathlons. The neurogenetic basis of the central governor requires further investigation.

MAOA gene polymorphisms and response to mirtazapine in major depression

Polymorphisms in the monoamine oxidase A (MAOA) gene may influence treatment outcomes in major depression disorder (MDD). To investigate the association of MAOA genetic polymorphisms and response to mirtazapine in patients with MDD. Fifty-eight adult patients in Taiwan who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnostic criteria for MDD were given mirtazapine for 7 weeks and evaluated on days 0, 7, 14, 21, 49 using the 24-item Hamilton Rating Scale for Depression (HRSD). Remission was defined as a final HRSD <or= 10 and a 50% reduction in baseline HRSD score. Patients provided venous blood for DNA testing. The patients' response to mirtazapine treatment was compared between those who had the long-form polymorphism in the MAOA gene promoter and the short-form polymorphism. The total HRSD scores after mirtazapine treatment were significantly lower than baseline (p < 0.001). There were 10 cases (38.5%) in short from and 6 (18.8%) in long from group touched the remission stage. Patients with the short-form group had a greater response to mirtazapine (p < 0.001) than those with the long-form polymorphism after controlling for age, sex, and apolipoprotein E genetic (APOE) polymorphism. The genetic polymorphisms in the MAOA promoter region may be associated with treatment response to mirtazapine.

Neither single-marker nor haplotype analyses support an association between monoamine oxidase A gene and bipolar disorder

Monoamine oxidase A (MAOA) abnormality has been suggested as a crucial factor in the pathogenesis of mood disorder, because MAOA is associated with the metabolism of monoamines such as serotonin and norepinephrine. Various MAOA gene polymorphisms have been investigated for possible associations with bipolar disorder (BD), but the results are controversial. Our goal was to investigate whether MAOA gene polymorphisms, especially the promoter uVNTR polymorphism and the EcoRV polymorphism, are associated either with BD or with different clinical subtypes of BD. A total of 714 Han Chinese subjects in Taiwan (305 controls and 409 BD patients) were recruited for study. All subjects were interviewed with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime; BD was diagnosed according to DSM-IV criteria. Genotyping for MAOA polymorphisms was performed using PCR and restriction fragment length polymorphism. The MAOA promoter polymorphisms uVNTR and EcoRV were not associated with BD or any of its subtypes, in either the frequencies of alleles or genotypes. In multiple logistic regression and haplotype frequency analysis, we confirmed these negative results in both females and males. Our results suggest that MAOA polymorphisms do not play a major role in pathogenesis of BD or its clinical subtypes in Han Chinese.

The association between fibromyalgia and polymorphism of monoamine oxidase A and interleukin-4

Because fibromyalgia (FM) is often comorbid with anxiety, and monoamine oxidase A (MAOA) was reported to be associated with anxiety, we determine if there is MAOA gene polymorphism associated with FM patients. Moreover, interleukin 4 (IL-4) was found to be an important cytokine participating in the immunologic pathway of T-helper 2 (Th-2) cells, in this study, we search if the genetic polymorphism of IL-4 intron3 could be demonstrated in FM patients. The genotype of sixty-two FM patients was compared with that of control subjects. The polymorphism of IL-4 intron3 variable number of tandem repeats (VNTR) was demonstrated by performing the genomic polymerase chain reaction (PCR) and analyzing the length of PCR product. Furthermore, the MAOA 941 G to T polymorphism was also determined by PCR-RFLP (restriction fragment length polymorphism) analysis. The MAOA 941 position genotype polymorphism between FM and control subjects was found neither statistically different in male (p=0.60) or female (p=0.52), nor total allelic frequency (p=0.52). Similarly, the difference of IL-4 intron3 polymorphism between FM and control was neither existing in genotype (p=0.06), nor allele frequency (p=0.07). The result suggests either the genetic linkage between FM and anxiety or that between FM and immunologic diseases are weak. Accordingly, the MAOA 941 position and IL-4 intron3 polymorphisms are not susceptible markers to predict FM.

No association between monoamine oxidase A promoter polymorphism and personality traits in Japanese females

Monoamine oxidase A (MAO-A) is an enzyme involved in the metabolism of monoamine neurotransmitters such as dopamine, serotonin, and noradrenaline in the brain. Previous studies have demonstrated a significant association between MAO-A gene polymorphism and personality traits in males. The purpose of the present study was to examine this association in females. The subjects were 219 healthy Japanese females. We genotyped a variable number of tandem repeats located upstream of the MAO-A gene. Personality traits were assessed using the Temperament and Character Inventory (TCI). There was no association between any personality trait and MAO-A genotype. The present results do not support the hypothesis that MAO-A gene polymorphism is related to certain personality traits in females.

Monoamine oxidase-A gene promoter polymorphism in female migraineurs

Objective: To assess whether there is a relationship between monoamine oxidase-A (MAOA) gene promoter polymorphism and migraine in female patients. Study design: A polymerase chain reaction based study in which MAOA promoter polymorphism was studied in 54 female migraineurs and 52 controls. Methods: The low (3-repeat) and high (one of 3.5, 4 or 5 repeat units) activity MAOA alleles were detected. The genotypes and allele frequencies were compared both within and between the groups. Results: The representation of both low (1/1) and high (2/2) activity genotypes were similar between the female migraineurs and controls. The allele frequencies were also similar between these groups. There was no relationship between the presence or absence of aura and MAO polymorphism. Conclusion: MAOA gene polymorphism is not associated with migraine or aura in female patients.

Monoamine oxidase-A gene polymorphism and antidepressant response to fluvoxamine in Japanese patients with major depressive disorder

Monoamine oxidase-A gene polymorphism and antidepressant response to fluvoxamine in Japanese patients with major depressive disorder