The serotonin transporter gene polymorphism is not associated with smoking behavior

Trummer, Olivia; Köppel, H; Wascher, Thomas C.; Grünbacher, Gerda; Gutjahr, M; Stanger, Olaf; Ramschak-Schwarzer, Sigrid; Boehm, Bernhard O.; Winkelmann, Bernhard R.; März, Winfried; Renner, Wilfried

doi:10.1038/sj.tpj.6500389

Cited by 32 publications

(30 citation statements)

References 23 publications

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“…Thus, polymorphisms present in the gene of the 5-HTT have been increasingly associated with the smoking habit in the last decade and the great majority of these search for association with the 5-HTTLPR polymorphism [30]. However, some research, such as the pioneer study by Lerman et al [31], did not report association of smoking behavior with the 5-HTTLPR polymorphism [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

“…In 2006, Trummer et al [30] suggested that other polymorphisms present in the SLC6A4 gene might be associated with smoking and the STin2 VNTR (5-HTTVNTR2) genetic variant was considered a promising candidate. There are various arguments for associating this polymorphism with smoking, such as the fact that it has a regulatory trait at the transcriptional level of the serotonin transporter, such as 5-HTTLPR.…”

Section: Discussionmentioning

confidence: 99%

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Association between the STin2 VNTR polymorphism and smoking behavior in oral cancer patients and healthy individuals

et al. 2011

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The serotonergic system may be involved in smoking behavior since the intake of nicotine increases serotonin secretion in the CNS. Moreover, evidence supporting the beneficial effect of selective serotonin reuptake for quitting smoking suggesting that the serotonin transporter (5-HTT) is a plausible target for the understanding and elucidation of smoking behavior. The transcriptional activity of its human gene (SLC6A4) is modulated by a polymorphism described in the second intron, the STin2 VNTR, which thus may interfere with 5-HTT synthesis. In this study was analyzed the polymorphism STin2 VNTR of 60 smokers male patients diagnosed for oral carcinoma, 61 male smokers without cancer and 65 non-smoker healthy blood donors. The STin2. 9 allele carriers were more present in smoker groups (with cancer and without cancer, respectively) than in the non-smoker (OR = 7.11, 95% CI = 0.83-60.91 and OR = 24.73; IC 95% = 3.17-192.66). Conversely, individuals carrying allele 10 were more prevalent in non-smokers compared with smokers (oral cancer patients and individuals without cancer, respectively), showing a protective factor of this allele (OR = 0.56; 95% CI = 0.24-1.33 and OR = 0.46; 95% CI = 0.20-1.07). This is the first report of a study assessing the importance of STin2 VNTR smoking behavior in Brazilian individuals and the association of STin2. 9 allele carriers in nicotine dependence. It is suggested that individuals with low serotonin concentration in the central nervous system, probably due to the presence of the allele for high expression of 5-HTT,especially STin2. 9, were more susceptible to nicotine dependence. Moreover, individuals with the 10 allele might have less risk for nicotine dependence.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association between the STin2 VNTR polymorphism and smoking behavior in oral cancer patients and healthy individuals

et al. 2011

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“…On balance, the 5-HTT promoter polymorphism seems not to be associated with smoking behavior. 69 The mechanisms underpinning the therapeutic effect of SSRIs remain incompletely understood. The knowledge that neuronal uptake blockade following antidepressant administration occurs rapidly but therapeutic effects may take from 2 to 6 weeks to occur 70 has been difficult to reconcile both in terms of the etiology of the disease and the therapeutic mechanism of SSRIs.…”

Section: Commentmentioning

confidence: 99%

Elevated Brain Serotonin Turnover in Patients With Depression

Barton¹,

Esler²,

Dawood³

et al. 2008

Arch Gen Psychiatry

190

107

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Context:The biological basis for the development of major depressive disorder (MDD) remains incompletely understood.Objective: To quantify brain serotonin (5-hydroxytryptamine ) turnover in patients with MDD.Design: Patients with depression were studied both untreated and during administration of a selective serotonin reuptake inhibitor (SSRI) in an unblinded study of sequential design. Healthy volunteers were examined on only 1 occasion. Direct internal jugular venous blood sampling was used to directly quantify brain serotonin turnover. The effect of serotonin transporter (5-HTT) genotype on brain serotonin turnover was evaluated and the influence of SSRI therapy on serotonin turnover was investigated.Setting: Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the research catheterization laboratory of a major training hospital and medical research institute. Conclusions: Brain serotonin turnover is elevated in unmedicated patients with MDD and is influenced by the 5-HTT genotype. The marked reduction in serotonin turnover following SSRI treatment and the accompanying improvement in symptoms suggest that high brain serotonin turnover may be a biological substrate of MDD. Psychiatry. 2008;65(1):38-46 T HE ETIOLOGY OF MAJOR DEpressive disorder (MDD) has been linked to brain monoaminergic neuronal dysfunction. Arch Gen1,2 Of particular interest is the role of brain serotonin (5-hydroxytryptamine [5-HT]) in MDD. The diversity of roles played by serotonin coupled with the lack of a demonstrated relationship between different clinical presentations and biochemical abnormalities has hampered the development of sensitive markers of the disease. Indeed, brain serotonin-releasing neurons subserve diverse although incompletely understood functions related to emotions and behavior, feeding and adiposity, 3 and light stimulation. 4 We have previously demonstrated influences of obesity and feeding 5 and season and sunlight 6 on brain serotonin turnover in humans. The principal means of intraneuronal metabolism of serotonin is via oxidative deamination by monoamine oxidase resulting in formation of 5-hydroxyindoleacetic acid (5-HIAA) (Figure 1). Deamination followed by reduction, conjugation with sulfate or glucuronide, and

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“…122 The evidence for the impact of 5-HTTLPR on smoking has been mixed; the S-allele occurred at a lower frequency in current smokers compared to former or never smokers, 123,124 but others have not found any associations with current smoking, age of smoking initiation, cigarette consumption, Fagerstrom Tolerance Questionaire (FTQ) scores or previous quit history. 125,126 Adolescents with the SS genotype were more likely to be current heavy smokers with earlier onset of smoking. 127 A strong relationship has been observed between the SS genotype and irritability levels, or temperament traits.…”

Section: Serotonin Systemmentioning

confidence: 99%

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

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The serotonin transporter gene polymorphism is not associated with smoking behavior

Cited by 32 publications

References 23 publications

Association between the STin2 VNTR polymorphism and smoking behavior in oral cancer patients and healthy individuals

Association between the STin2 VNTR polymorphism and smoking behavior in oral cancer patients and healthy individuals

Elevated Brain Serotonin Turnover in Patients With Depression

Overview of the pharmacogenomics of cigarette smoking

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