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Association Analysis of a Regulatory Variation of the Serotonin Transporter Gene with Severe Alcohol Dependence
Author(s) -
Sander Thomas,
Harms Helmut,
Lesch KlausPeter,
Dufeu Peter,
Kuhn Silke,
Hoehe Margret,
Rommelspacher Hans,
Schmidt Lutz G.
Publication year - 1997
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1997.tb04462.x
Subject(s) - serotonin transporter , genotype , delirium , allele , odds ratio , alcohol dependence , medicine , polymorphism (computer science) , genetics , biology , psychiatry , gene , alcohol , biochemistry
The present study tested the hypothesis that the short, low activity variant of a biallelic polymorphism in the 5’regulatory region of the human serotonin transporter (5‐HTT) gene confers susceptibility to severe alcohol dependence marked by severe withdrawal symptoms. Applying a phenotype‐genotype strategy, our population‐based association analysis included 216 German controls and an extreme sample of 103 severely affected alcoholics who were selected from 315 German alcohol‐dependent subjects by a history of alcohol withdrawal seizure or delirium. The frequency of the short allele (S) was significantly increased in the severely affected alcoholics, compared with that in the controls ( X 2 = 3.87, df = 1, nominal p = 0.049). The post‐hoc exploration indicated that this allelic association resulted exclusively from a significant excess of the S/S genotype in the severely affected alcoholics ( p = 0.035), suggesting a recessively acting effect. Consistently, we found a weak but significant correlation ( p = 0.013) between the frequency of the S/S genotype and severity of withdrawal symptoms (WDS): no WOS [18.3%, odds ratio (OR) = 1.16], vegetative WDS only (21.8%, OR = 1.44), and severe WDS with either withdrawal seizure only or delirium only (25.0%, OR = 1.69), and both withdrawal seizure and delirium (30.8%, OR = 2.30). Further studies are required to test whether the tentative genotype‐phenotype relationship occurred by chance or reflects a real genotypic association between a recessively modifying effect of the short variant of the functional 5‐HTT promoter polymorphism and alcohol withdrawal vulnerability.