Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism

Wang, Tzu Yun; Lee, Sheng-Yu; Chang, Yun-Hsuan; Chen, Shih‐Heng; Chu, Chun-Hsien; Huang, San-Yuan; Tzeng, Nian‐Sheng; Wang, Chen-Lin; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru‐Band

doi:10.1186/1744-9081-8-18

Cited by 18 publications

(14 citation statements)

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“…We found no association between the 5-HTTLPR polymorphism and alcohol and opiate dependence in the current study, after an attempt was made to reduce the heterogeneity by excluding the comorbidity of antisocial personality, since addicts with antisocial personality may have different genetic vulnerabilities than do pure substance abusers [55] . Study results focused on the 5-HTTLPR polymorphism and alcohol and opiate dependence are controversial [24,[26][27][28][29][30][31] .…”

Section: -Httlpr S+: Scontrasting

confidence: 73%

“…Second, our alcohol-dependent and opiate-dependent patients were all recruited from hospitals, not from prisons. In our prior studies of alcoholism [55] , we found that the genetic background in patients with alcoholism was different from that of patients with antisocial personality disorder. Whether the effect of the TPH1 and 5-HTTLPR genes still is relevant in patients with antisocial personality disorder also requires additional studies.…”

Section: -Httlpr S+: Smentioning

confidence: 90%

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TPH1 and 5-HTTLPR Genes Specifically Interact in Opiate Dependence but Not in Alcohol Dependence

et al. 2016

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Background: Different drug dependencies may have unique genetic vulnerabilities. Changes in serotonin availability and function have been linked to addiction. We investigated whether 2 serotonergic polymorphisms, TPH1 A218C (rs1800532) and 5-HTT-linked promoter region (5-HTTLPR) (rs25531), are differently associated with alcohol or opiate dependence. Methods: Alcohol-dependent patients (n = 292), opiate-dependent patients (n = 309), and healthy controls (n = 301) were recruited from the Han Chinese population in Taiwan. Genotypes of TPH1 A218C and 5-HTTLPR polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. Results: The genotype frequencies of the TPH1 A218C polymorphisms were not significantly different in the 3 groups. The genotype frequencies of the 5-HTTLPR S+ (S/S, S/L_G, L_G/L_G) polymorphisms were significantly higher in opiate-dependent patients (χ² = 8.77, p = 0.01), but not after controlling for the covariates of age, gender, and interaction effect in logistic regression analysis. Moreover, there was a significant interaction between the TPH1 A218C A/C and 5-HTTLPR S+ gene polymorphisms in opiate-dependent (OR 2.72, p = 0.01), but not in alcohol-dependent patients. Conclusions: Our data suggested that there may be a differential genetic vulnerability in serotonergic genes for alcohol and opiate addiction. However, replications of our findings are still needed.

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Section: -Httlpr S+: Scontrasting

confidence: 73%

Section: -Httlpr S+: Smentioning

confidence: 90%

TPH1 and 5-HTTLPR Genes Specifically Interact in Opiate Dependence but Not in Alcohol Dependence

et al. 2016

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“…These studies were then filtered to ensure conformity with the inclusion criteria. Four studies (Foley et al, 2004;Galeeva et al, 2002;Pastorelli et al, 2001) were excluded because no diagnostic criteria was described explicitly; one study (Munafo et al, 2005) because it was investigating social 'drinkers' rather than alcohol-dependent or abusing subjects; one study (Rasmussen et al, 2009) because it investigated alcohol and cigarette consumption rather than dependence or abuse; three studies (Budde et al, 2010;Mingione et al, 2012;Thompson et al, 2010) because no matched control data were described; and two studies Hallikainen et al, 1999;Hammoumi et al, 1999;Hill et al, 2002;Ishiguro et al, 1999;Johann et al, 2003;Kohnke et al, 2006;Konishi et al, 2004;Kranzler et al, 2002;Lee et al, 2009;Lichtermann et al, 2000;Marques et al, 2006;Matsushita et al, 2001;Mokrovic et al, 2008;Namkoong et al, 2008;Nellissery et al, 2003;Parsian and Cloninger, 2001;Philibert et al, 2008;Preuss et al, 2001;Reese et al, 2010;Saiz et al, 2009;Samochowiec et al, 2006;Sander et al, 1998;Sander et al, 1997;Shin et al, 2009;Stoltenberg et al, 2002;Thompson et al, 2000;Wang et al, 2012;Wang et al, 2011b;Wu et al, 2008) investigated alcohol dependence or abuse. Among them...…”

Section: Resultsmentioning

confidence: 99%

Multi-Cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

Cao

Hudziak

2013

Neuropsychopharmacol

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A number of studies have reported associations between the serotonin transporter gene (SLC6A4) and alcohol, heroin, cocaine, or methamphetamine abuse. Other studies have yielded contrary results. There are a number of reasons for non-replication, including inadequate statistical power, population stratification, and poor phenotype definition. This study was to test the association using a meta-analytic approach across a variety of racial and ethnic populations. Using the genotype data of 55 studies (7999 cases, 8264 controls, and 676 families or parent-offspring trios) published in the past 15 years, we have conducted comprehensive meta-analyses to examine the associations of the 5-HTTLPR and STin2 polymorphisms with substance use disorder. The meta-analyses support the associations of 5-HTTLPR with alcohol, heroin, cocaine, and methamphetamine dependence and abuse (eg, the smallest P-values were 0.0058 with odds ratio (OR) ¼ 0.54 (0.35, 0.84); 0.0024 with OR ¼ 0.77 (0.66, 0.91); 0.018 with OR ¼ 1.38 (1.06, 1.81); and 0.028 with OR ¼ 0.46 (0.23, 0.92) for alcohol, heroin, cocaine, and methamphetamine dependence/abuse, respectively). When all the phenotypes are combined, the P-value was 0.0006 with OR ¼ 0.86 (0.78, 0.94) in the combined European, Asian, and Mexican populations and P-value was 0.0028 with OR ¼ 1.41 (1.13, 1.78) in the African populations. Evidence of significant associations was also identified in other subgroup analyses regarding differently combined substance and populations. The effect sizes of 5-HTTLPR were comparable among the European, Asian, and Mexican populations, however, the risk allele was more frequent in Asians than in Europeans and Mexicans. The opposite directions of risk allele in African population might be driven by the opposite directions of risk allele in cocaine dependence. This meta-analysis supports that the association of the SLC6A4 gene with substance use disorder varies depending on substances with different risk allele frequencies in the multi-cultural populations. Further studies using larger sample size are warranted.

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“…The risk allele 5-HTTLPR S was significantly more frequent in Asians (73%) than in Europeans (43%) and Mexicans (53%), whereas the 5- HTTLPR L allele was the risk allele in African populations [46]. One study in a Han Chinese population reported that alcohol-dependent patients were more likely to carry the low-functional genotypes of 5-HTTLPR, such as SS, SL G , or L G L G [47], while other studies which considered triallelic functional 5-HTTLPR found no such association between the selected SNP and alcohol dependence [48]. Evidence from animal and human studies supports a role for 5 - HTTLPR gene-environment interactions in the development of excessive alcohol intake [49,50].…”

Section: Discussionmentioning

confidence: 99%

Alcohol Dependence and Genetic Variability in the Serotonin Pathway among Currently and Formerly Alcohol-Dependent Males

et al. 2015

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Background: Genes involved in the serotonin pathway may determine the susceptibility to alcohol dependence and its severity. The present study explored whether specific polymorphisms in the serotonin pathway could be associated with alcohol dependence or alcohol-related psychopathological symptoms. Methods: The cohort comprised 101 currently and 100 formerly alcohol-dependent males, as well as 97 male healthy blood donors. The following questionnaires were employed: the Alcohol Use Disorders Identification Test, the Zung Depression and Anxiety Scale, the Brief Social Phobia Scale, the Yale-Brown Obsessive Compulsive Scale and Obsessive Compulsive Drinking Scale, and the Buss-Durkee Hostility Inventory. Subjects were genotyped for bi- and triallelic SLC6A4 5-HTTLPR,HTR1A rs6295, and HTR1B rs13212041. Results: Statistical differences in bi- and triallelic SLC6A4 5-HTTLPR genotype distribution were observed between the 3 groups investigated (p = 0.008 and p = 0.023, respectively); however, no gene-dose effect was observed. The severity of the alcohol problems was higher in currently alcohol-dependent subjects with the 5-HTTLPR LL (p = 0.039) and L′L′ genotypes (p = 0.027). Formerly dependent subjects with the 5-HTTLPR S′S′ genotype showed more social anxiety, depressive, and anxiety traits (p = 0.009, p = 0.006, and p = 0.036, respectively). Healthy controls with the 5-HTTLPR SS genotype showed more traits of social anxiety (p = 0.020). Conclusions: Our findings suggest that bi- and triallelic SLC6A4 5-HTTLPR has some effects on the severity of alcohol dependence. Triallelic 5-HTTLPR was associated with social anxiety, anxiety, and depressive traits in alcohol-dependent subjects.

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Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism

Cited by 18 publications

References 75 publications

<b><i>TPH1</i></b> and <b><i>5-HTTLPR</i></b> Genes Specifically Interact in Opiate Dependence but Not in Alcohol Dependence

<b><i>TPH1</i></b> and <b><i>5-HTTLPR</i></b> Genes Specifically Interact in Opiate Dependence but Not in Alcohol Dependence

Multi-Cultural Association of the Serotonin Transporter Gene (SLC6A4) with Substance Use Disorder

Alcohol Dependence and Genetic Variability in the Serotonin Pathway among Currently and Formerly Alcohol-Dependent Males

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