Differential role of serotonergic polymorphisms in alcohol and heroin dependence

Sáiz, Pilar A.; García-Portilla, María Paz; Flórez, Gerardo; Arango, Celso; Corcoran, Paul; Morales, Blanca; Bascarán, María Teresa Bobes; Álvarez, César Soriano; Narciso, Gema San; Carreño, Eduardo; Álvarez, Victoria; Coto, Eliécer; Bobes, Julio

doi:10.1016/j.pnpbp.2009.03.016

Cited by 37 publications

(26 citation statements)

References 56 publications

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“…We therefore propose that such serotonin deficiency seems to be exclusively related to opiate but not alcohol dependence. Our data support the findings of Tsuang et al [3] that genetic vulnerability to dependence is drug-specific, and of Saiz et al [31] that serotoninergic genes are involved in the development of opiate dependence. Further study is required to clarify the different roles of serotonin dysfunction in the different classes of addiction.…”

Section: Discussionsupporting

confidence: 92%

“…SPECT studies of humans also showed that L/L carriers had an increased availability of raphe serotonin transporter [24] and higher serotonin transporter mRNA levels than S/S and S/L carriers [25] . Although the S allele has been associated with alcoholism [26,27] and opiate dependence [28] , this association is still controversial [24,[29][30][31] . In addition to the past dichotomous classification of 5-HTTLPR into the S and L alleles, the L allele have been reported with more complicated sub-classification [32,33] .…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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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“…In a German study conducted among 250 institutionalized alcoholics and 94 healthy controls, no significant differences were observed with respect to S and L allele genotypes between the two groups (Kohnke et al 2006). Similarly, in a Spanish study of 165 alcohol-dependent patients, 113 heroine-dependent patients and 420 healthy controls, Saiz et al (2009) showed that there were no associations between 5-HTTLPR polymorphism and alcohol dependence. Rasmussen et al (2009) studied an elderly population of women with a history of severe alcoholism and also found no association between 5-HTTLPR polymorphism and alcohol dependence.…”

Section: -Httlpr Polymorphism and Alcohol Use Problemsmentioning

confidence: 89%

A review of 5-HT transporter linked promoter region (5-HTTLPR) polymorphism and associations with alcohol use problems and sexual risk behaviors

et al. 2015

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Alcohol use and sexual risk behaviors are multidimensional phenomena involving many genetic and environmental factors. 5-HT transporter linked promoter region (5-HTTLPR) polymorphism constitutes an important factor affecting alcohol use problems and risky sexual behaviors. This paper narratively reviews studies on 5-HTTLPR polymorphism and its associations with alcohol use problems and sexual risk behaviors. We searched the electronic databases, PubMed, Ovid, and Google Scholar for articles using MeSH terms. Relevant articles were reviewed and eligible articles were selected for the study. Many studies have reported a significant but moderate association between 5-HTTLPR polymorphism and alcohol use problems. These studies have implicated the presence of at least one S allele to be associated with significant increases in alcohol use problems. Similarly, some studies associate the S allele with increased sexual risk behaviors. Effective alcohol cessation initiatives and STI/HIV prevention programs should be modified to account for 5-HTTLPR polymorphism before planning interventions; genetic effects could moderate the intervention effect.

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Differential role of serotonergic polymorphisms in alcohol and heroin dependence

Cited by 37 publications

References 56 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

A review of 5-HT transporter linked promoter region (5-HTTLPR) polymorphism and associations with alcohol use problems and sexual risk behaviors

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