A meta-analysis of the associations between the SLC6A4 promoter polymorphism (5HTTLPR) and the risk for alcohol dependence

Abstract

Serotonin reuptake variation is linked to a functional polymorphism in the promoter region of the SLC6A4 gene on chromosome 17. It is plausible that variations in genetically determined SLC6A4 activity may modify the risk of alcohol dependence. To determine whether this allele is associated with alcohol dependence, the authors conducted a systematic review and a metaanalysis. Twenty five studies with 8,885 participants were included. The meta-analysis was conducted using a random-effects model. Overall, the results did not support the association between alcohol dependence and SLC6A4 promoter polymorphism for the dominant, recessive . When effect modification was tested for gender, race/ethnicity, presence/absence of a psychiatric disorder, year of publication, and diagnostic criteria, none of the factors were significantly associated with alcohol dependence. The findings in this meta-analysis suggest that SLC6A4 promoter polymorphism is not associated with alcohol dependence.

Childhood adversities and 5-HTTLPR polymorphism as risk factors of substance use disorders: retrospective case-control study in Murcia (Spain)

“…The third showed a significant association of SUDs (including alcohol, heroin and cocaine dependence) with the polymorphism 11. Finally, the most recent meta-analysis did not find an overall association with alcohol dependence, but highlighted several methodological limitations in published studies19 including: inconsistencies in the screening of highly comorbid psychiatric disorders, lack of an adequate control group as many of the studies relied on convenience samples rather than population-based controls, insufficient description of genotyping methods and heterogeneity in case definition.…”

“…An a priori decision was made not to correct for multiple testing as conditions in which a correction for multiple testing is necessary are still a matter of controversy. It has been suggested that in exploratory analyses of a genetically complex trait in which the relationship between genotype and phenotype has not yet been established,11 17–19 44 multiple test adjustments are not strictly required45 since they may increase the likelihood that actual effects would be missed (type II error rates) 46…”

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

“…A limitation of this study is that the groups were not appropriately matched according to age and years of education, which could have had an impact on the study results. We compensated for potential gender differences in drinking behavior [70,71] by including only male subjects, thus further increasing the strength of our study, although a recently published meta-analysis found no influence of sex and SLC6A4 5-HTTLPR on alcohol dependence [72]. Our study was also not biased by genetic heterogeneity, since we included only Slovenian subjects recruited in a geographic area with an ethnically homogeneous Caucasian population [73,74].…”

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

“…For example, a meta-analysis of 25 case control studies (n=8885) found no link between 5-HTTLPR polymorphism and alcoholism (Villalba et al 2015). 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).…”