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

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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An X chromosome inactivation assay based on differential methylation of a CpG island coupled to a VNTR polymorphism at the 5′ end of the monoamine oxidase A gene

Human Molecular Genetics ◽

10.1093/hmg/1.3.187 ◽

1992 ◽

Vol 1 (3) ◽

pp. 187-194 ◽

Cited By ~ 31

Author(s):

Rudolf W. Hendriks ◽

Zheng-Yi Chen ◽

Heather Hinds ◽

Ruud K. B. Schuurman ◽

Ian W. Craig

Keyword(s):

Monoamine Oxidase ◽

X Chromosome ◽

Cpg Island ◽

X Chromosome Inactivation ◽

Differential Methylation ◽

Monoamine Oxidase A ◽

Chromosome Inactivation ◽

Vntr Polymorphism

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An X chromosome inactivation assay based on differential methylation of a CpG island coupled to a VNTR polymorphism at the 5′ end of the Monoamine Oxidase A gene

Human Molecular Genetics ◽

10.1093/hmg/1.8.662 ◽

1992 ◽

Vol 1 (8) ◽

pp. 662-662 ◽

Cited By ~ 6

Author(s):

R.W. Hendriks ◽

Z.-Y. Chen ◽

H. Hinds ◽

R.K.B. Schuurman ◽

I.W. Craig

Keyword(s):

Monoamine Oxidase ◽

X Chromosome ◽

Cpg Island ◽

X Chromosome Inactivation ◽

Differential Methylation ◽

Monoamine Oxidase A ◽

Chromosome Inactivation ◽

Vntr Polymorphism

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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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