Gacek Paul, Conner Tamlin S, Tennen Howard, Kranzler Henry R, Covault Jonathan
Public Health Program, Department of Community Medicine and Health Care, University of Connecticut Health Center, Farmington, CT 06030-6325, USA.
Addict Biol. 2008 Sep;13(3-4):440-8. doi: 10.1111/j.1369-1600.2008.00118.x.
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 a 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. 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 show that 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. In conclusion, 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.
调节血清素活性的基因被视为大量饮酒的有前景的预测指标。色氨酸羟化酶(TPH2)在血清素能神经传递中发挥重要作用,它是中脑和血清素能神经元中血清素生物合成的限速酶。尽管TPH2与血清素能功能之间存在联系,但其在酒精使用障碍发病机制中的作用仍不清楚。本研究的目的是检验TPH2基因的变异是否与危险饮酒有关。具体而言,本研究检验了TPH2基因G-703T多态性是否能预测大学生的饮酒情况。在连续两年的时间里,351名本科生被要求使用基于互联网的电子日记,连续30天每天记录他们的饮酒情况。收集参与者的DNA并进行聚合酶链反应基因分型。结果表明,饮酒与单独的TPH2 G-703T多态性、TPH2与其他两个候选多态性(TPH1 C218A和SLC6A4三等位基因5-HTTLPR)的相互作用或负面生活事件均无关联。总之,本研究支持了最近关于TPH2与饮酒结果无关的研究结果。它还通过表明在预测美国白人年轻成年人亚临床饮酒方面,TPH2与TPH1 C218A多态性、SLC6A4三等位基因5-HTTLPR多态性和环境应激源之间不存在相互作用,扩展了这些发现。