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SLC6A4 S/S

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https://www.readbyqxmd.com/read/29220746/testing-bidirectional-relationships-between-alcohol-use-and-depressive-symptoms-what-is-the-role-of-the-serotonin-transporter-gene
#1
Roy Otten, Carmen S van der Zwaluw, Rutger C Engels
Alcohol abuse often co-exists with a major depressive disorder. In order to understand the development of this comorbidity, it is important to concentrate on the preceding process. It has been suggested that the link between alcohol use and depressive symptoms is a result of an interaction with genetic factors. The aim of this study was to longitudinally examine the effect of the 5-HTTLPR genotype on the association between depressive symptoms and alcohol use in a Dutch community sample. Following a stepwise approach, bivariate correlations, longitudinal regression analyses, and latent growth curve analyses were separately conducted for 316 males and 321 females...
August 13, 2017: Alcohol
https://www.readbyqxmd.com/read/28972592/genetically-driven-brain-serotonin-deficiency-facilitates-panic-like-escape-behavior-in-mice
#2
J Waider, S Popp, M D Lange, R Kern, J F Kolter, J Kobler, N C Donner, K R Lowe, J H Malzbender, C J Brazell, M R Arnold, B Aboagye, A Schmitt-Böhrer, C A Lowry, H C Pape, K P Lesch
Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings...
October 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28892067/association-of-the-serotonin-transporter-linked-polymorphic-region-genotype-with-lower-bone-mineral-density
#3
M I Lapid, S Kung, M A Frye, J M Biernacka, J R Geske, M T Drake, M D Jankowski, B L Clarke
The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) S allele is linked to pathogenesis of depression and slower response to selective serotonin reuptake inhibitors (SSRIs); depression and SSRIs are independently associated with bone loss. We aimed to determine whether 5-HTTLPR was associated with bone loss. This cross-sectional study included psychiatric patients with both 5-HTTLPR analysis and bone mineral density (BMD) assessment (hip and spine Z-scores if age <50 years and T-scores if ⩾50 years)...
August 22, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28888667/preimmunization-with-a-heat-killed-preparation-of-mycobacterium-vaccae-enhances-fear-extinction-in-the-fear-potentiated-startle-paradigm
#4
James H Fox, James E Hassell, Philip H Siebler, Mathew R Arnold, Andrew K Lamb, David G Smith, Heidi E W Day, Tessa M Smith, Emma M Simmerman, Alexander A Outzen, Kaley S Holmes, Christopher J Brazell, Christopher A Lowry
The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits, and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for trauma-related, anxiety, and affective disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience...
September 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28842491/conformational-state-interactions-provide-clues-to-the-pharmacochaperone-potential-of-serotonin-transporter-partial-substrates
#5
Shreyas Bhat, Peter S Hasenhuetl, Ameya Kasture, Ali El-Kasaby, Michael H Baumann, Bruce E Blough, Sonja Sucic, Walter Sandtner, Michael Freissmuth
Point mutations in SLC6 transporters cause misfolding, which can be remedied by pharmacochaperones. The serotonin transporter (SERT/SLC6A4) has a rich pharmacology including inhibitors, releasers (amphetamines, which promote the exchange mode), and more recently, discovered partial substrates. We hypothesized that partial substrates trapped the transporter in one or several states of the transport cycle. This conformational trapping may also be conducive to folding. We selected naphthylpropane-2-amines of the phenethylamine library (PAL) including the partial substrate PAL1045 and its congeners PAL287 and PAL1046...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28766852/serotonin-transporter-promoter-polymorphism-modulates-the-ability-to-control-food-intake-effect-on-total-weight-loss
#6
Gemma Bonnet, Purificación Gómez-Abellán, Beatriz Vera, Juan Francisco Sánchez-Romera, Antonio M Hernández-Martínez, Silvia Sookoian, Carlos Jose Pirola, Marta Garaulet
SCOPE: The biggest challenge for losing weight is the ability to control the amount of food eaten; the tendency to overeat is called disinhibition. Our aims were to determine whether (a) the SLC6A4-promoter variant (5-HTTLPR) relates to disinhibition; (b) this association could affect total weight-loss during a behavioral/dietary treatment for obesity. METHODS AND RESULTS: A total of 2961 subjects attended voluntarily five weight-loss clinics; a subsample (n = 624) was recruited for SLC6A4 genotyping...
August 2, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28719342/a-pilot-study-for-determination-of-anxiety-related-slc6a4-promoter-s-and-l-alleles-in-healthy-turkish-athletes
#7
A Corak, S Kapici, C Sercan, O Akkoç, K Ulucan
We aimed to analyze the allelic distribution of solute carrier family-6 member-4 promoter region in Turkish athletes. Recent studies showed the association of lesser expressing "S" allele with anxiety. Genotype percentages for LL, LS and SS genotypes were found as 46, 35 and 19, respectively. 38% of the males had LL, %38 had LS and 24% had SS genotypes. Percentages of LL, LS and SS genotypes were 54, 31 and 15 in females, respectively. 15 (58%) male and 18 (69%) females had L, 11 (42%) male and 8 (31%) females had S alleles...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28675387/serotonin-transporter-gene-promoter-methylation-status-correlates-with-in-vivo-prefrontal-5-htt-availability-and-reward-function-in-human-obesity
#8
M Drabe, M Rullmann, J Luthardt, Y Boettcher, R Regenthal, T Ploetz, G A Becker, M Patt, C Schinke, F T Bergh, F Zientek, A Hilbert, A Bresch, W Fenske, M K Hankir, O Sabri, S Hesse
A polymorphism in the promoter region of the human serotonin transporter (5-HTT)-coding SLC6A4 gene (5-HTTLPR) has been implicated in moderating susceptibility to stress-related psychopathology and to possess regulatory functions on human in vivo 5-HTT availability. However, data on a direct relation between 5-HTTLPR and in vivo 5-HTT availability have been inconsistent. Additional factors such as epigenetic modifications of 5-HTTLPR might contribute to this association. This is of particular interest in the context of obesity, as an association with 5-HTTLPR hypermethylation has previously been reported...
July 4, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28670115/the-influence-of-the-serotonergic-system-on-the-personality-and-quality-of-life-of-postmenopausal-women
#9
Daria Schneider-Matyka, Anna Jurczak, Małgorzata Szkup, Agnieszka Samochowiec, Anna Grzywacz, Sylwia Wieder-Huszla, Elżbieta Grochans
The aim of this study was to establish the relationship between personality traits of postmenopausal women and the presence of the 44-bp VNTR polymorphism in the serotonin transporter (5-HTT) (SLC6A4) promoter region and the 30-bp VNTR polymorphism in the MAO-A promoter region. The study's aim was also to determine the influence of personality traits on the quality of postmenopausal women's lives. The study involved 214 postmenopausal women from northwest Poland, with an average age of 56.8±4.08 years. It was performed using the Temperament and Character Inventory-Revised and the Short Form Health Survey...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28654193/serotonin-transporter-gene-polymorphisms-and-selective-serotonin-reuptake-inhibitor-tolerability-review-of-pharmacogenetic-evidence
#10
REVIEW
Jing Zhu, Michele Klein-Fedyshin, James M Stevenson
Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy for mood and anxiety disorders. The common mechanism of drugs in this class is antagonism of the serotonin transporter. Within the serotonin transporter gene SLC6A4, two polymorphic sites termed 5-HTTLPR and STin2 are proposed to have functional consequences and thus have been attractive candidates for pharmacogenetic studies of SSRI efficacy and tolerability. This review summarizes approximately 15 years of study of these polymorphisms as they relate to SSRI tolerability phenotypes...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28650965/epigenetic-adaptation-of-the-placental-serotonin-transporter-gene-slc6a4-to-gestational-diabetes-mellitus
#11
Sofia Blazevic, Marina Horvaticek, Maja Kesic, Peter Zill, Dubravka Hranilovic, Marina Ivanisevic, Gernot Desoye, Jasminka Stefulj
We tested the hypothesis that gestational diabetes mellitus (GDM) alters the DNA methylation pattern of the fetal serotonin transporter gene (SLC6A4), and examined the functional relevance of DNA methylation for regulation of the SLC6A4 expression in the human placenta. The study included 50 mother-infant pairs. Eighteen mothers were diagnosed with GDM and 32 had normal glucose tolerance (NGT). All neonates were of normal birth weight and born at term by planned Cesarean section. DNA and RNA were isolated from samples of tissue collected from the fetal side of the placenta immediately after delivery...
2017: PloS One
https://www.readbyqxmd.com/read/28639488/prenatal-exposure-to-serotonin-reuptake-inhibitors-and-congenital-heart-anomalies-an-exploratory-pharmacogenetics-study
#12
Aizati N A Daud, Jorieke E H Bergman, Wilhelmina S Kerstjens-Frederikse, Pieter van der Vlies, Eelko Hak, Rolf M F Berger, Henk Groen, Bob Wilffert
AIM: To explore the role of pharmacogenetics in determining the risk of congenital heart anomalies (CHA) with prenatal use of serotonin reuptake inhibitors. METHODS: We included 33 case-mother dyads and 2 mother-only (child deceased) cases of CHA in a case-only study. Ten genes important in determining fetal exposure to serotonin reuptake inhibitors were examined: CYP1A2, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC6A4, HTR1A, HTR1B, HTR2A and HTR3B. RESULTS: Among the exposed cases, polymorphisms that tended to be associated with an increased risk of CHA were SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 and rs6298 and HTR3B rs1176744, but none reached statistical significance due to our limited sample sizes...
June 22, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28576508/a-review-of-the-role-of-serotonin-system-genes-in-obsessive-compulsive-disorder
#13
REVIEW
Vanessa M Sinopoli, Christie L Burton, Sefi Kronenberg, Paul D Arnold
Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder that causes the patient to experience intrusive thoughts and/or to carry out repetitive, ritualized behaviors that are time consuming and impairing. OCD is familial and heritable. The genetic factors responsible for pathogenesis, however, remain largely unknown despite the numerous candidate gene studies conducted. Based on efficacy of serotonin reuptake inhibitors (SRIs) in treating OCD, serotonin system genes have been a dominant focus in OCD candidate gene studies...
May 30, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28316763/serotonin-transporter-gene-slc6a4-polymorphism-and-mucosal-serotonin-levels-in-southeastern-iranian-patients-with-irritable-bowel-syndrome
#14
Mojgan Mohammadi, Hossein Tahmasebi Abdar, Hamid Reza Mollaei, Hossein Hajghani, Mohammad Reza Baneshi, Mohammad Mahdi Hayatbakhsh
BACKGROUND Irritable bowel syndrome (IBS) is a digestive system disorder with an unknown etiology. Serotonin has a key role in the secretion and motility of the intestine. Polymorphism in serotonin re-uptake transporter (SERT or SLC6A4) gene may have a functional role in the gut of patients with IBS. The aims of the present study were to investigate the association between SLC6A4 gene polymorphism and IBS and to detect the correlation between rectal serotonin levels and IBS sub-types. METHODS SLC6A4 gene polymorphism in 131 patients with IBS and 211 healthy controls were analysed using the quantitative polymerase chain reaction high-resolution melting (qPCR-HRM) curve technique...
January 2017: Middle East Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28262188/effects-of-the-serotonin-transporter-gene-sensitivity-of-response-to-alcohol-and-parental-monitoring-on-risk-for-problem-alcohol-use
#15
Lora M Cope, Emily C Munier, Elisa M Trucco, Jillian E Hardee, Margit Burmeister, Robert A Zucker, Mary M Heitzeg
The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) has been previously associated with alcohol-related risk. Most findings point to short (S) allele carriers being at increased risk for negative alcohol outcomes relative to long allele homozygotes, although some work indicates a more complex relationship. The current prospective study aimed to clarify how and under what circumstances variations in 5-HTTLPR transmit risk for various alcohol-related outcomes...
March 2017: Alcohol
https://www.readbyqxmd.com/read/28137459/systematic-review-and-meta-analysis-of-genetic-studies-of-late-life-depression
#16
REVIEW
Ruby S M Tsang, Karen A Mather, Perminder S Sachdev, Simone Reppermund
Late-life depression (LLD) is thought to be multifactorial in etiology, including a significant genetic component. While a number of candidate gene studies have been carried out, results remain inconclusive. We undertook a systematic review of all genetic association studies of depression or depressive symptoms in late life published before February 2016, and performed meta-analyses on polymorphisms investigated in three or more independent studies. A total of 46 candidate gene studies examining 56 polymorphisms in 23 genes as well as a genome-wide association study (GWAS) were included...
April 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28068779/norepinephrine-transporter-gene-variants-and-remission-from-depression-with-venlafaxine-treatment-in-older-adults
#17
MULTICENTER STUDY
Victoria S Marshe, Malgorzata Maciukiewicz, Soham Rej, Arun K Tiwari, Etienne Sibille, Daniel M Blumberger, Jordan F Karp, Eric J Lenze, Charles F Reynolds, James L Kennedy, Benoit H Mulsant, Daniel J Müller
OBJECTIVE: The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine. METHOD: The sample included 350 adults age 60 or older with DSM-IV-defined major depressive disorder and a score of at least 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS)...
May 1, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/27989490/paraphilic-sexual-offenders-do-not-differ-from-control-subjects-with-respect-to-dopamine-and-serotonin-related-genetic-polymorphisms
#18
Andrzej Jakubczyk, Aleksandra Krasowska, Marcin Bugaj, Maciej Kopera, Anna Klimkiewicz, Agata Łoczewska, Aneta Michalska, Aleksandra Majewska, Natalia Szejko, Anna Podgórska, Małgorzata Sołowiej, Leszek Markuszewski, Sławomir Jakima, Rafał Płoski, Kirk Brower, Marcin Wojnar
INTRODUCTION: Rape and pedophilic child molestation are the most commonly convicted sexual offenses in Poland. Recent studies have suggested a possible genetic contribution toward pathologic sexual interests and behaviors. AIM: To analyze and compare functional polymorphisms of genes associated with the activity of the serotonin and dopamine systems in a group of paraphilic sexual offenders and control subjects. METHODS: The study sample (n = 97) consisted of two groups: paraphilic sexual offenders (65 pedophilic child molesters and 32 rapists) and controls (n = 76)...
January 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27743374/associations-between-genetic-risk-functional-brain-network-organization-and-neuroticism
#19
Michelle N Servaas, Linda Geerligs, Jojanneke A Bastiaansen, Remco J Renken, Jan-Bernard C Marsman, Ilja M Nolte, Johan Ormel, André Aleman, Harriëtte Riese
Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on neuroticism. The aim of the current study was to investigate how genetic risk factors impact functional network organization and whether genetic risk factors moderate the association between neuroticism and functional network organization...
October 14, 2016: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/27509352/impulsive-choices-in-mice-lacking-imprinted-nesp55
#20
C L Dent, T Humby, K Lewis, A Plagge, R Fischer-Colbrie, J F Wilkins, L S Wilkinson, A R Isles
Genomic imprinting is the process whereby germline epigenetic events lead to parent-of-origin specific monallelic expression of a number of key mammalian genes. The imprinted gene Nesp is expressed from the maternal allele only and encodes for Nesp55 protein. In the brain, Nesp55 is found predominately in discrete areas of the hypothalamus and midbrain. Previously, we have shown that loss of Nesp55 gives rise to alterations in novelty-related behaviour. Here, we extend these findings and demonstrate, using the Nesp(m/+) mouse model, that loss of Nesp55 leads to impulsive choices as measured by a delayed-reinforcement task, whereby Nesp(m/+) mice were less willing to wait for a delayed, larger reward, preferring instead to choose an immediate, smaller reward...
November 2016: Genes, Brain, and Behavior
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