Association of Functional Polymorphism in TPH2 Gene with Alcohol Dependence and Personality Traits: Study in Cloninger's Type I and Type II Alcohol-Dependent Inpatients.

Abstract

Alcohol dependence (AD) is a complex disorder with a poorly understood etiology. In this study, we investigated the relationship between genetic variation in the TPH2 gene, which encodes the enzyme responsible for serotonin synthesis in the brain, and both AD and personality traits, with attention to Cloninger's types of AD. The study included 373 healthy control subjects, 206 inpatients with type I AD, and 110 inpatients with type II AD. All subjects were genotyped for the functional polymorphism rs4290270 in the TPH2 gene, and AD patients completed the Tridimensional Personality Questionnaire (TPQ). The AA genotype and the A allele of the rs4290270 polymorphism were more frequent in both patient groups compared with the control group. In addition, a negative association was found between the number of A alleles and TPQ scores for harm avoidance in patients with type II, but not type I, AD. These results support the involvement of genetic variations of the serotonergic system in the pathogenesis of AD, especially type II AD. They also suggest that in a subset of patients, genetic variation of TPH2 could potentially influence the development of AD by affecting the personality trait of harm avoidance.