Gizatullin Rinat, Zaboli Ghazal, Jönsson Erik G, Asberg Marie, Leopardi Rosario
Department of Clinical Neuroscience, Psychiatry Section, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
J Affect Disord. 2008 Apr;107(1-3):175-9. doi: 10.1016/j.jad.2007.07.005. Epub 2007 Aug 10.
Serotonin (5-HT) has been implicated in the pathophysiology of several psychiatric disorders including major depression (MD). Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin (5-HT), and might be related to the pathogenesis of MD. Two isoforms are known, TPH-1 and TPH-2. Their association with MD is still debated.
A case-control design was used for candidate gene-disease association in 194 patients with stress-induced MD, and 246 healthy controls, all North European Caucasians. Five TPH-2 polymorphisms were analyzed in terms of genotype, allele, and haplotype-based associations.
Neither single marker nor haplotype-based analyses showed significant associations between TPH-2 and MD.
The interpretations are limited by the restricted population size.
There was no association between TPH-2 gene variants and MD in the same population that had shown a strong association with TPH-1. Hence, the results suggest that in this particular group of stress-induced depression patients TPH-1 appears to be more relevant to MD pathogenesis than TPH-2.
血清素（5-羟色胺，5-HT）与包括重度抑郁症（MD）在内的多种精神疾病的病理生理学有关。色氨酸羟化酶（TPH）是血清素（5-HT）生物合成中的限速酶，可能与重度抑郁症的发病机制有关。已知有两种亚型，即TPH-1和TPH-2。它们与重度抑郁症的关联仍存在争议。
采用病例对照设计，对194例应激性重度抑郁症患者和246名健康对照者（均为北欧白种人）进行候选基因与疾病的关联研究。从基因型、等位基因和单倍型关联方面分析了5种TPH-2多态性。
单标记分析和基于单倍型的分析均未显示TPH-2与重度抑郁症之间存在显著关联。
研究结果的解释受到样本量有限的限制。
在同一人群中，TPH-2基因变异与重度抑郁症之间无关联，而该人群中TPH-1与重度抑郁症有很强的关联。因此，结果表明，在这一特定组应激性抑郁症患者中，TPH-1似乎比TPH-2与重度抑郁症发病机制更相关。
