Feinn R, Nellissery M, Kranzler HR. Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 133: 79-84
The neurotransmitter serotonin (5-HT) has been shown to regulate alcohol consumption in both animals and humans. Since activity of the 5-HT transporter protein (5-HTT) regulates 5-HT levels, the gene encoding this protein may contribute to the risk of alcohol dependence (AD). Studies of the association to AD of a functional insertion-deletion polymorphism in the 5-HTT-linked promoter region (5-HTTLPR) have yielded inconsistent results. We conducted a meta-analysis of data from 17 published studies (including 3,489 alcoholics and 2,325 controls) investigating the association between 5-HTTLPR alleles and AD. The frequency of the short (S) allele at 5-HTTLPR was significantly associated with AD [odds ratio (OR) = 1.18, 95% CI = 1.03-1.33). Moreover, a greater association with the S allele was seen among individuals with AD complicated by either a co-morbid psychiatric condition or an early-onset or more severe AD subtype [OR = 1.34 (95% CI = 1.11-1.63)]. Allelic variation at 5-HTTLPR contributes to risk for AD, with the greatest effect observed among individuals with a co-occurring clinical feature.
"As a result, additional pharmacogenetic studies that carefully phenotype participants are needed to guide clinical care. Because many studies have found the S allele to be associated with AD concurrent with an Axis I disorder (Thompson et al., 2000; Feinn et al., 2005; McHugh et al., 2010; Herman and Balogh, 2012), it seems paradoxical that treatment response to SSRIs may be greater in patients with one or two L alleles. This phenomenon may result from the increased expression of 5-HTT associated with the L allele and present opportunities for the development of SSRI drugs with improved transporter binding. "
Alcohol and Alcoholism 08/2015; DOI:10.1093/alcalc/agv090 · 2.89 Impact Factor
"Recently published review of candidate gene-based studies, linkage studies and genome-wide association studies pointed out a limited role of individual genetic variants in the risk for alcohol dependence, although single risk variants within neurotransmitter signalling pathways may help to deepen the understanding of the underlying pathophysiology of alcohol dependence . Serotonin (5-HT) has been shown to regulate alcohol consumption in both animals and humans and is considered to be involved in many aspects of alcohol consumption, abuse and dependence . Studies investigating alcohol use disorders have recently focused on the neuronal tryptophan hydroxylase 2 (TPH2) gene . "
"However the association with specific alleles remained inconsistent, with variations according to alcohol subtype, type of drinking behavior, ethnicity, comorbid diagnoses or age of onset. Findings of meta-analyses that have examined the role of the 5-HTTLPR in AD indicated that there was a significant but modest association with the S allele (Feinn et al., 2005; McHugh et al., 2010; Cao et al., 2013). "
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