Promoter Region Of Monoamine Oxidase Research Articles

Post-Stroke Fatigue May Be Associated with the Promoter Region of a Monoamine Oxidase A Gene Polymorphism

Background: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. Methods: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A). Results: Among the 373 patients, 164 (44%) had PSF. All patients were ethnic Koreans. Of the 6 polymorphisms examined, only one marker, that is, low-activity MAO-A was associated with PSF (p < 0.05) in female patients. Multiple logistic regression analyses showed that post-stroke depression (PSD; 95% CI 1.561-14.323, p = 0.006) and low MAO-A activity (95% CI 0.166-0.722, p = 0.005) were factors associated with PSF in female patients, whereas only PSD (95% CI 5.511-65.269, p = 0.000) was associated with PSF in male patients. Conclusions: Our findings suggest that PSF may be associated with a genetic polymorphism involving MAO-A, at least in female stroke patients.

Susceptibility to methamphetamine dependence associated with high transcriptional activity alleles of VNTR polymorphism in the promoter region of monoamine oxidase A (MAOA)

Background and purposeMonoamine oxidase A (MAOA, Xp11.3; OMIM: 309850) can modulate the level of neurotransmitters in the central nervous system. A 30bp variable number of tandem repeat (VNTR) genetic polymorphism on the promoter region of the MAOA can modulate the transcriptional activity of the gene. Association between this polymorphism and dependency to methamphetamine was investigated. Subjects and methodsA total of 65 methamphetamine abusers (52 males and 13 females) and 635 healthy controls (525 males and 110 females) were included in the present case–control study. Genotypic analysis for the MAOA VNTR polymorphism was determined by conventional PCR. Based on transcriptional activity of the VNTR alleles, the alleles were categorized into two classes: L allele (2R and 3R alleles) and H allele (3.5R, 4R and 5R alleles), which have low and high transcriptional activities, respectively. ResultsOur data show that the H allele significantly increases the risk of methamphetamine dependence in males (OR=2.03, 95% CI: 1.04–3.67, P=0.037). The H allele seems positively associated with the risk of dependency to methamphetamine among females, but the observed OR did not reach the significance level, probability due to small sample size of the patients. ConclusionThe present study supports the role of the VNTR polymorphism on the promoter region of the MAOA on methamphetamine dependence.

Influence of serotonergic/noradrenergic gene polymorphisms on nausea and sweating induced by milnacipran in the treatment of depression

The present study was conducted to find out the predictors of side effects such as nausea and excessive sweating induced by milnacipran, a serotonin/norepinephrine reuptake inhibitor. Both clinical characteristics prior to the treatment and gene polymorphisms such as serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the second intron of the 5-HTT gene (5-HTTVNTR), 5-HT2A receptor gene (5-HT2A G-1438A), a TPH gene polymorphism in intron 7 (TPH A218C), norepinephrine transporter (NET) gene polymorphism in the promoter region (NET T-182C) and in the exon 9 (NET G1287A), a variable number of tandem repeats in the promoter region of monoamine oxidase A, were items to be assessed in this study. Ninety-six patients with major depressive disorder were treated with milnacipran. Side effects were assessed at 1, 2, 4, and 6 weeks of treatment with Udvalg for Kliniske Undersogelser side effects scale. The results showed that no gene polymorphisms included in this study affected the susceptibility of nausea and excessive sweating induced by milnacipran. Patients with older age are more likely to develop excessive sweating than others. The major limitation of this study is a small sample size. Further studies with larger populations and more kinds of gene polymorphisms should be needed to see if specific gene polymorphisms determine the susceptibility of side effects induced by milnacipran.

What is an “Adverse” Environment? Interactions of Rearing Experiences and MAOA Genotype in Rhesus Monkeys

Studies have been inconsistent in demonstrating that early adversity and specific genotype can be joint risk factors for poor behavioral outcomes. Using a rhesus monkey model, we examined how social context and different forms of early adversity influence whether a specific genotype (polymorphism in the promoter region of monoamine oxidase A [MAOA]) affects display of aggressive, fearful, and anxious behaviors. Rhesus monkey infants (n = 473) were exposed to brief social challenge at age 3-4 months. Infants were reared 1) with mothers and up to 150 other animals in large cages; 2) with mothers in smaller social groups; 3) with mother and access to, at most, one other mother-infant pair; and 4) without mother but with access to a same-age peer in a nursery. No effects of genotype were found for infants reared by mothers in large social cages, although several genotype by rearing environment interactions were evident. Animals reared in smaller social groups were more likely to display aggression, which was especially true of animals possessing the low-activity MAOA genotype. In addition, animals with low-activity genotypes that had experienced restricted mother rearing showed more anxious behavior (scratch, yawn). Among mother-reared animals, broader contextual features, associated with the social environment and experience of the mother, can affect the extent to which genotype contributes to behavioral expression under conditions of challenge. Results also suggest that different forms of early adverse experience can affect the types of responses displayed by animals of different genotypes.

Functional variation in promoter region of monoamine oxidase A and subtypes of alcoholism: haplotype analysis.

Monoamine oxidase (MAO) is a mitochondrial enzyme involved in the degradation of certain neurotransmitter amines. MAO-A, due to its function in central nervous system, has been one of the important candidate genes involved in the development of neuropsychiatric disorders. A functional polymorphism in the promoter region of the MAO-A gene has been identified. This variation affects the transcriptional efficiency of the gene. To determine the role of this MAO-A functional polymorphism in the development of subtypes of alcoholism, a sample of alcoholics and normal controls were screened with this marker. The allele frequency differences between total alcoholics, Types I and II alcoholics, and normal controls was not significant. Comparison of male alcoholics to male normal controls for the frequencies of two-loci and three-loci haplotypes was statistically significant. After Bonferroni's correction for multiple tests none of the results remained significant at P < 0.05. Our results indicate that MAO-A may play a role in the development of alcoholism but the gene effect is very small.

Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism

We analyzed a novel functional 30-bp repeat polymorphism in the promoter region of the X-chromosomal monoamine oxidase A gene ( MAOA) to test whether length variation of the repeat polymorphism contributes to variation in the individual vulnerability to antisocial behavior and liability to alcohol dependence. The repeat number (3–5) of the MAOA polymorphism was assessed in 488 male subjects of German descent, a sample comprising 185 psychiatrically screened control subjects and 303 alcohol-dependent subjects including 59 alcoholics with antisocial personality disorder. The frequency of the low-activity 3-repeat allele was significantly increased in 59 antisocial alcoholics compared to 185 control subjects (51 vs. 35%; P=0.031) and to 244 alcoholics without antisocial personality disorder (51 vs. 32%; P=0.008), respectively. We found no significant difference in the frequency of the 3-repeat allele between 244 alcoholics without an antisocial personality disorder and the control subjects. Our findings suggest that the low-activity 3-repeat allele of the MAOA promoter polymorphism confers increased susceptibility to antisocial behavior rather than alcohol dependence per se in alcohol-dependent males.