Genetic Variation in the Vesicular Monoamine Transporter 1 (<i>VMAT1/SLC18A1</i>) Gene and Alcohol Withdrawal Severity

Dutta, Nisha; Helton, Sarah G.; Schwandt, Melanie L.; Zhu, Xi; Momenan, Reza; Lohoff, Falk W.

doi:10.1111/acer.12991

Cited by 13 publications

(6 citation statements)

References 40 publications

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“…Lohoff concluded that VMAT1 variants play a role in emotional processing as well as risk for psychopathology. These findings buttress association studies showing that the minor A allele of VMAT1 variant rs1390938 has been associated with lower risk of alcohol use dependence (Dutta et al, 2016;Vaht, Kiive, Veidebaum, & Harro, 2016), anxiety-related personality traits (Lohoff et al, 2008), maladaptive impulsivity, anxiety, depressiveness, and neuroticism (Vaht et al, 2016). Closely related VMAT2 (SLC18A2) SNPs have been associated with phenotypes such as depression in elderly men (Christiansen et al, 2007), alcohol dependence (Schwab et al, 2005), and posttraumatic stress disorder (Solovieff et al, 2014).…”

Section: Vesicular Monoamine Transportersmentioning

confidence: 72%

Genetic correlates of spirituality/religion and depression: A study in offspring and grandchildren at high and low familial risk for depression.

Anderson¹,

Miller²,

Wickramaratne³

et al. 2017

Spirituality in Clinical Practice

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Rationale Possible genetic correlates of spirituality and depression have been identified in community samples. We investigate some of the previously identified candidates in a sample of families at both high and low-risk for depression. Method Offspring and grandchildren of individuals at high and low-risk for depression, participating in a multi-wave thirty-year longitudinal study, were assessed for seven SNPS drawn from four single gene candidates associated with systems implicated in both depression and spirituality: Serotonin (5-HT1B and 5-HT2A), Dopamine (DRD2), Oxytocin (OT) and Monoamine Vesicular Transporter (VMAT1). Results Dopamine (DRD2) Serotonin (5-HT1B), their Transporter (VMAT1) and Oxytocin (OXTR) were positively associated with a high level of importance of spirituality or religion (S/R) in the group at low familial risk for depression. DRD2 minor allele was associated with both lifetime major depressive disorder (MDD) and spirituality in the low-risk group for depression. No SNPs were related to S/R in the group at high familial risk for depression. OXTR was associated with lifetime MDD in the full sample. Conclusion Genes for dopamine, serotonin, their vesicular transporter, and oxytocin may be associated with S/R in people at low familial risk for depression. Genes for dopamine may be associated both with S/R and increased risk for depression in people at low-risk for depression, suggesting a common pathway or physiology to mild to moderate depression. MDD is associated with oxytocin across risk groups. In the high-risk group, phenotypic expression of S/R may be suppressed. Implications The shared association of DRD2 by S/R and depression, generally found to be inversely related, calls for further research on their common physiological pathways, and the phenotypic expression of these pathways based upon use and environment. Prevention for offspring at high familial risk for depression might include support for the development of child spirituality.

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Section: Vesicular Monoamine Transportersmentioning

confidence: 72%

Genetic correlates of spirituality/religion and depression: A study in offspring and grandchildren at high and low familial risk for depression.

Anderson¹,

Miller²,

Wickramaratne³

et al. 2017

Spirituality in Clinical Practice

View full text Add to dashboard Cite

show abstract

“…Genetic changes in VMAT1 could thus affect the amount of monoamines contained in vesicles, which is in turn released from the nerve terminal, affecting downstream signaling. A recent study has shown that VMAT1 knockout in mice lead to differential dopamine signaling [52], and several other studies have revealed the association of the 136Thr with a variety of psychiatric phenotypes including alcohol dependence [38, 53], bipolar disorders [34], autism [39], anxiety [37, 38], maladaptive impulsivity, depressiveness, and neuroticism [38]. A functional neuroimaging study has revealed that this variant has distinct influences on activity of the prefrontal cortex and amygdala [44], both of which play crucial roles in emotional processing, that may underlie the socioemotional differences observed in the abovementioned studies.…”

Section: Discussionmentioning

confidence: 99%

Human-specific mutations in VMAT1 confer functional changes and multi-directional evolution in the regulation of monoamine circuits

et al. 2019

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BackgroundNeurochemicals like serotonin and dopamine play crucial roles in human cognitive and emotional functions. Vesicular monoamine transporter 1 (VMAT1) transports monoamine neurotransmitters, and its variant (136Thr) is associated with various psychopathological symptoms and reduced monoamine uptake relative to 136Ile. We previously showed that two human-specific amino acid substitutions (Glu130Gly and Asn136Thr/Ile) of VMAT1 were subject to positive natural selection. However, the potential functional alterations caused by these substitutions (Glu130Gly and Asn136Thr) remain unclear. To assess functional changes in VMAT1 from an evolutionary perspective, we reconstructed ancestral residues and examined the role of these substitutions in monoamine uptake in vitro using fluorescent false neurotransmitters (FFN), which are newly developed substances used to quantitatively assay VMATs.ResultsImmunoblotting confirmed that all the transfected YFP-VMAT1 variants are properly expressed in HEK293T cells at comparable levels, and no significant difference was seen in the density and the size of vesicles among them. Our fluorescent assays revealed a significant difference in FFN206 uptake among VMAT1 variants: 130Glu/136Asn, 130Glu/136Thr, and 130Gly/136Ile showed significantly higher levels of FFN206 uptake than 130Gly/136Asn and 130Gly/136Thr, indicating that both 130Glu and 136Ile led to increased neurotransmitter uptake, for which 136Thr and 136Asn were comparable by contrast.ConclusionsThese findings suggest that monoamine uptake by VMAT1 initially declined (from 130Glu/136Asn to 130Gly/136Thr) in human evolution, possibly resulting in higher susceptibility to the external environment of our ancestors.

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“…SLC18A1 maps to chromosome 8p23.1, a region of genes associated with personality traits (21). SLC18A1 rs1390938/Thr136Ile is associated with mood, depression, personality, and alcohol use in the general population (22,23). Individuals homozygous for the 'hyperfunction' allele (AA; Ile/Ile) appear to be more resilient to these disorders (24).…”

Section: Discussionmentioning

confidence: 99%

Expression of the Vesicular Monoamine Transporter Gene Solute Carrier Family 18 Member 1 (SLC18A1) in Lung Cancer

Lehrer¹,

Rheinstein²

2018

Cancer Genomics Proteomics

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Most never-smokers with lung cancer do not respond to immune checkpoint inhibitors (ICIs). But for unknown reasons, a small proportion do show clinical benefit from the ICI pembrolizumab. Because of the good response of this group, it may be worthwhile assessing their SLC18A1 expression pre-treatment as a marker for potential clinical benefit. If SLC18A1 expression is low, a never-smoker may respond well to ICIs. High levels of expression would indicate a C5 tumor less likely to respond to ICIs. SLC18A1 might complement other biomarkers currently under study in relation to programmed cell death protein 1/programmed cell death protein ligand 1 inhibition.

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Genetic Variation in the Vesicular Monoamine Transporter 1 (VMAT1/SLC18A1) Gene and Alcohol Withdrawal Severity

Cited by 13 publications

References 40 publications

Genetic correlates of spirituality/religion and depression: A study in offspring and grandchildren at high and low familial risk for depression.

Genetic correlates of spirituality/religion and depression: A study in offspring and grandchildren at high and low familial risk for depression.

Human-specific mutations in VMAT1 confer functional changes and multi-directional evolution in the regulation of monoamine circuits

Expression of the Vesicular Monoamine Transporter Gene Solute Carrier Family 18 Member 1 (SLC18A1) in Lung Cancer

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