GENETIC STUDY: Tryptophan hydroxylase 2 gene and alcohol use among college students

Abstract

Objective-Genes that regulate serotonin activity are regarded as promising predictors of heavy alcohol use. Tryptophan Hydroxylase (TPH2) plays an important role in serotonergic neurotransmission by serving as the rate-limiting enzyme for serotonin biosynthesis in the midbrain and serotonergic neurons. Despite the link between TPH2 and serotonergic function, TPH2's role in the pathogenesis of alcohol use disorders remains unclear. The goal of this study was to examine whether variation in the TPH2 gene is associated with risky alcohol consumption. Specifically, this study examined whether the TPH2 G-703T polymorphism predicted alcohol consumption among college students.Methods-In two successive years, 351 undergraduates were asked to record their alcohol use each day for 30 days using an internet-based electronic diary. Participants' DNA was collected and polymerase chain reaction genotyping was performed.Results-Alcohol consumption was not associated with the TPH2 G-703T polymorphism alone, or the interaction of TPH2 with two other candidate polymorphisms (TPH1 C218A, and the SLC6A4 tri-allelic 5-HTTLPR) or negative life events.Conclusions-This study supports recent null findings relating TPH2 to drinking outcomes. It also extends these findings by showing null interactions with the TPH1 C218A polymorphism, the SLC6A4 tri-allelic 5-HTTLPR polymorphism, and environmental stressors in predicting sub-clinical alcohol use among Caucasian American young adults.

Congenital brain serotonin deficiency leads to reduced ethanol sensitivity and increased ethanol consumption in mice

“…Thus, our data suggest that genetic mutations leading to brain 5-HT deficiency, including functional mutations in Tph2 , could contribute to the development of alcoholism, at least in a subset of patients. It should be noted that several studies examining the associations between polymorphisms in Tph2 and alcoholism have yielded negative results (Zill et al, 2007; Gacek et al, 2008), but it is possible that further analyses examining additional polymorphisms or that specifically examine functional polymorphisms may reveal significant associations. In addition, 5-HT deficiency or impaired functioning of the 5-HT system could result from mutations in a variety of genes other than Tph2 .…”

Functional polymorphisms in the serotonin 1B receptor gene (HTR1B) predict self‐reported anger and hostility among young men

“…To avoid population stratification, we limited the analysis sample to individuals of non-Hispanic Caucasian ancestry. This sample included individuals analyzed elsewhere for unrelated hypotheses (Armeli et al, 2008; Covault et al, 2007; Gacek et al, 2008; Gunthert et al, 2007). The average age of sample participants at the start of this four-year study was 18.7 +/ 0.9 yrs with 61% percent freshmen, 32% sophomores, and 7% upper classmen.…”

Pharmacogenetics of Drug Dependence: Role of Gene Variations in Susceptibility and Treatment

“…Polymorphisms within intron 7 of the TPH1 gene were found to be associated with increased risk for alcohol dependency in different ethnic groups (70,71). However, studies have consistently reported a lack of association between TPH2 and alcoholism (72,73).…”