Association between serotonin transporter gene polymorphisms and heroin dependence: a meta-analytic study

Lin, Pao‐Yen; Wu, Y.‐K.

doi:10.2147/ndt.s120786

Cited by 7 publications

(5 citation statements)

References 41 publications

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“…Although there are likely multiple contributing factors in developing substance dependences, including multiple genes with subtle effects, this study was focused on the tandem repeats in the functional polymorphism in the SERT promoter (5-HTTLPR) in a cohort of subjects of European ancestry from the Netherlands, including subjects with current opioid dependence, lifetime opioid use without opioid dependence, and healthy controls. In contrast to some previous findings showing a significant association of heroin dependence with the S allele of 5-HTTLPR in Caucasians, 20 , 22 , 23 we did not find a significant association of short (S) or long (L) forms of the repeats with the categorical opioid dependence diagnosis. Reasons for this discrepancy include methodological differences.…”

Section: Discussioncontrasting

confidence: 99%

“…There were no differences in the reduction in cocaine use across the LL, LS and SS genotypes, in African-American patients with cocaine dependence. 20 Studies of cocaine dependence diagnosis as a categorical endpoint did not detect a robust association with 5-HTTLPR genotype, either in Spanish 24 or African-American cohorts. 25 In another study, carriers of the S allele reported greater “desire” and other subjective effects after challenge with intravenous cocaine injection.…”

Section: Introductionmentioning

confidence: 92%

“… 15 The 5-HTTLPR (ie, 5-HTT length promoter polymorphic region) has been investigated in numerous genetic association studies, 16–21 including systematic reviews on the role of 5-HTTLPR on substance use disorders and their pharmacotherapy. 20 , 22 …”

Section: Introductionmentioning

confidence: 99%

“… 23 A meta-analyses of the 5-HTTLPR allele and genotype frequencies in Caucasians showed that heroin dependence diagnosis was significantly associated with the S allele. 20 The 5-HTTLPR polymorphism has also been examined in several studies of cocaine use disorders. There were no differences in the reduction in cocaine use across the LL, LS and SS genotypes, in African-American patients with cocaine dependence.…”

Section: Introductionmentioning

confidence: 99%

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Association of Serotonin Transporter (SERT) Polymorphisms with Opioid Dependence and Dimensional Aspects of Cocaine Use in a Caucasian Cohort of Opioid Users

Yuferov

Butelman

Randesi

et al. 2021

NDT

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Introduction A functional tandem repeat polymorphism in the promoter of the serotonin transporter (SERT) gene (SLC6A4) has been studied for association to neuropsychiatric conditions, including substance use disorders. Short (S) forms of this repeat result in reduced transcription, and presumably greater synaptic levels of serotonin, which are involved in opioid and cocaine-induced reward. Dual exposure to heroin and cocaine is a common pattern of poly-drug use and is associated with considerable morbidity. We hypothesize that SLC6A4 variants are associated with cocaine exposure in subjects with an opioid dependence diagnosis (OD), and also in non-dependent opioid users (NOD). Other single nucleotide polymorphisms (SNPs) of SLC6A4 may also be likewise associated. Materials and Methods This study determined whether variants of the SLC6A4 promoter repeats and two intronic SNPs, rs16965628 and rs2066713, are associated with categorical diagnoses of opioid dependence (DSM-IV criteria) and with dimensional aspects of cocaine use, in a Caucasian cohort (n=591). Three groups of subjects were examined: (1) 276 subjects with opioid dependence diagnosis (OD); (2) 163 subjects who had used opioids for non-medical reasons but never had an opioid dependence diagnosis (NOD); (3) 152 healthy controls (HC). Results Aside from high exposure to heroin in the OD group, relatively high exposure to cocaine was detected in both OD and NOD groups. The SERT repeat genotype (classified as “long-long” [LL] versus ”short-long” plus “short-short” [SL+SS]) was not associated with categorical opioid dependence diagnoses. A nominally signiﬁcant association was identiﬁed with the [SL+SS] genotype of SLC6A4 and cocaine KMSK scores ≥“cutpoint” for a cocaine dependence diagnosis ( p =0.026). The [SL+SS] genotype was associated with more rapid cocaine escalation than the LL genotype. No signiﬁcant associations of rs16965628 and rs2066713 SNPs were found overall. Conclusion The functional SERT promoter tandem repeat genotype may be associated to heavy cocaine exposure and more rapid escalation of cocaine use, in persons with and without opioid dependence diagnosis.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of Serotonin Transporter (SERT) Polymorphisms with Opioid Dependence and Dimensional Aspects of Cocaine Use in a Caucasian Cohort of Opioid Users

Yuferov

Butelman

Randesi

et al. 2021

NDT

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“…According to a meta-analysis by Lin and Wu [35], the 'S' allele has been found to be more common in the opioid-dependent population. The 'S' allele has reduced transcriptional activity and is associated with impulsive behavior, suicidal attempts, and violent behavior.…”

Section: Discussionmentioning

confidence: 99%