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

4557 Background: In patients with metastatic midgut carcinoid tumors increased serotonin secretion is related to the carcinoid syndrome and mortality. Free serotonin is taken up via the serotonin transporter (5-HTT) in the liver and the lung and metabolized to 5- hydroxyindolacetic acid (5-HIAA) by Monoamine Oxidase A (MAO-A). The 5-HTT gene has a functional polymorphism in the promoter region (5-HTTPLR), with a short (S, less active) and long (L) allele and a polymorphic region in the second intron with variable number tandem repeats (VNTR-2). The MAO-A gene contains a length polymorphism in its promoter region (MAOA-LPR). To determine the clinical effects of the serotonin metabolizing capacity of individual patients, the association between different genotypes and symptoms (flushes and diarrhea) and survival was studied. Methods: 107 patients with metastatic midgut carcinoid tumors were genotyped for 5-HTTPLR, VNTR-2 and MAO-A-LPR. Differences were tested using Chi-square test and survival according to genotypes was analyzed using Kaplan Meier survival curves and tested with a log rank test. The independent effect of genotypes on survival was studied with multivariate Cox regression analysis with adjustments for the urinary 5-HIAA level, age at presentation and the presence of liver metastases. Results: The various genotypic variants were not related to flushes or diarrhea. Patients with the SS variant of 5-HTTLPR had a shorter median survival (45 months, 95% Confidence Interval (CI) 0.50–90) compared to patients with the LS (113 months, 95% CI 53–172) and the LL variant (90 months, 95% CI 64–115) (P=0.02). After adjustment, survival in patients with the SS variant remained worse with an odds ratio of 0.43 (95% CI 0.23–0.83; P=0.009) and 0.63 (95% CI 0.33–1.11; P=0.1) compared to patients with the LS and the LL variant respectively. Survival was not influenced by the VNTR-2 or MAOA-LPR. Conclusions: The SS genotype of the 5-HTTLPR is independently associated with a worse survival in patients with metastatic midgut carcinoid tumors. No significant financial relationships to disclose.

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

Egyptian Journal of Medical Human Genetics ◽

10.1016/j.ejmhg.2015.08.004 ◽

2016 ◽

Vol 17 (1) ◽

pp. 111-114

Author(s):

Khyber Saify ◽

Mostafa Saadat

Keyword(s):

Monoamine Oxidase ◽

Promoter Region ◽

Transcriptional Activity ◽

Monoamine Oxidase A ◽

High Transcriptional Activity ◽

Vntr Polymorphism ◽

Methamphetamine Dependence

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

Cerebrovascular Diseases ◽

10.1159/000450894 ◽

2016 ◽

Vol 43 (1-2) ◽

pp. 54-58 ◽

Cited By ~ 8

Author(s):

Smi Choi-Kwon ◽

Mihye Ko ◽

Sang-Eun Jun ◽

Juhan Kim ◽

Kyung-Hee Cho ◽

...

Keyword(s):

Monoamine Oxidase ◽

Promoter Region ◽

Tryptophan Hydroxylase ◽

Variable Number Tandem Repeat ◽

Variable Number ◽

Monoamine Oxidase A ◽

Potential Contribution ◽

Female Patients ◽

Post Stroke ◽

Mao A

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.

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Family-based and population study of a functional promoter-region monoamine oxidase A polymorphism in autism: Possible association with IQ

American Journal of Medical Genetics ◽

10.1002/ajmg.10189 ◽

2002 ◽

Vol 114 (3) ◽

pp. 284-287 ◽

Cited By ~ 27

Author(s):

Nurit Yirmiya ◽

Tammy Pilowsky ◽

Sigal Tidhar ◽

Lubov Nemanov ◽

Larissa Altmark ◽

...

Keyword(s):

Monoamine Oxidase ◽

Population Study ◽

Promoter Region ◽

Monoamine Oxidase A ◽

Family Based

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VNTR polymorphism in the monoamine oxidase A promoter region and cerebrospinal fluid catecholamine concentrations in forensic autopsy cases

Neuroscience Letters ◽

10.1016/j.neulet.2019.02.029 ◽

2019 ◽

Vol 701 ◽

pp. 71-76

Author(s):

Aya Matsusue ◽

Shin-ichi Kubo ◽

Tomoya Ikeda ◽

Naoto Tani ◽

Toshiki Maeda ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Monoamine Oxidase ◽

Promoter Region ◽

Monoamine Oxidase A ◽

Forensic Autopsy ◽

Vntr Polymorphism

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Association between variable number of tandem repeats (VNTR) polymorphism in the promoter region of monoamine oxidase A (MAOA) gene and susceptibility to heroin dependence

Psychiatry Research ◽

10.1016/j.psychres.2015.08.017 ◽

2015 ◽

Vol 229 (3) ◽

pp. 1055-1056 ◽

Cited By ~ 3

Author(s):

Khyber Saify ◽

Mostafa Saadat

Keyword(s):

Monoamine Oxidase ◽

Promoter Region ◽

Tandem Repeats ◽

Variable Number ◽

Heroin Dependence ◽

Monoamine Oxidase A ◽

Maoa Gene ◽

Vntr Polymorphism

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Association of variable number of tandem repeats (VNTR) and T941G polymorphism of monoamine oxidase (MAO-A) gene with aggression in Pakistani subjects

African Health Sciences ◽

10.4314/ahs.v21i1.24 ◽

2021 ◽

Vol 21 (1) ◽

pp. 180-8

Author(s):

Sumbal Sarwar ◽

Shabana ◽

Shahida Hasnain

Keyword(s):

Monoamine Oxidase ◽

Promoter Region ◽

Tandem Repeats ◽

Variable Number ◽

Monoamine Oxidase A ◽

Pakistani Population ◽

Behavioral Traits ◽

Genotype Frequencies ◽

Pcr Rflp ◽

Mao A

Background: Human behavioral traits are known to be significantly heritable. Certain individuals have a greater tendency of negative behavioral aspects including aggression. The quest to identify tunderlying genetic causes has led to identification of a number of genetic markers, one of them is the monoamine oxidase-A (MAO-A) gene. Objective: We aimed to genotype a variable number of tandem repeats (VNTRs) in the promoter region and a functional SNP within this gene (T941G, dbSNP ID: rs6323) in the recruited cohort of 482 subjects. Methods: After DNA isolation, genotyping was done by PCR-RFLP and the results were confirmed by sequencing. Results: For VNTRs, the results showed, highest frequency of 3.5 repeats in males and 4 repeats in females in the promoter region. The genotype frequencies for the SNP in cases were GG=16.3%, TG=20.6% and TT=63.1%, while in controls, the frequencies were GG=12.7%, TG=6.3%, and TT=81.0%. The allele frequencies were significantly different between cases and controls (p=0.015; OR=1.51; CI=1.085-2.102). Conclusion: The selected VNTR and SNP appeared to be significantly associated with aggression. These VNTRs and SNP have not been studied previously in the Pakistani population, hence they represent a unique ethnic group. These results, however, would have to be replicated in larger cohorts. Keywords: Aggression; MAO-A gene; VNTRs; T941G; rs6323; Pakistan.

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