Grabe Hans Jörgen, Spitzer Carsten, Schwahn Christian, Marcinek Agnes, Frahnow Antje, Barnow Sven, Lucht Michael, Freyberger Harald Jürgen, John Ulrich, Wallaschofski Henri, Völzke Henry, Rosskopf Dieter
Department of Psychiatry, Ernst-Moritz-Arndt-University of Greifswald, HANSE-Klinikum Stralsund, Rostocker Chaussee 70, Stralsund, Germany.
Am J Psychiatry. 2009 Aug;166(8):926-33. doi: 10.1176/appi.ajp.2009.08101542. Epub 2009 Jun 1.
There has been debate whether polymorphisms within the serotonin transporter-linked polymorphic region (5-HTTLPR) moderate susceptibility to posttraumatic stress disorder (PTSD). The authors investigated 5-HTTLPR genotypes and their interaction with the number of traumatic events in the prediction of PTSD in a general population sample.
Analyses were based on data from 3,045 subjects who participated in the Study of Health in Pomerania. All participants were assessed with the PTSD module of the Structured Clinical Interview for DSM-IV. The short (S)/long (L) polymorphism of 5-HTTLPR (rs4795541) and the A-G polymorphism (rs25531) were genotyped.
Among the participants, 1,663 had been exposed to at least one traumatic event, and 67 (4.0%) developed PTSD. Among those who had experienced less than three traumatic events, the lifetime prevalence of PTSD was 2.6%, 3.5%, and 4.3% for those with zero, one, and two L(A) alleles, respectively, but the lifetime prevalence was 0%, 7.3%, and 19.6%, respectively, among those with three or more traumatic experiences. This finding suggests that there is an additive excess risk for frequent trauma in the L(A)/L(A) genotype, which was confirmed by the relative excess risk due to interaction (RERI). In allelic analysis, RERI was 3.3. Thus, the odds ratio for PTSD in L(A) allele carriers exposed to three or more traumas was 3.3 times higher as a result of the interaction between PTSD and the L(A) allele.
An additive gene-environment interaction with the high expression L(A) allele of 5-HTTLPR and frequent trauma in PTSD was found. The attributable proportion indicated that more than 60% of all L(A) allele carriers who were exposed to three or more traumas developed PTSD as a result of an interaction between genotype and exposure.
关于血清素转运体相关多态性区域（5-HTTLPR）内的多态性是否会调节创伤后应激障碍（PTSD）的易感性一直存在争议。作者在一个普通人群样本中研究了5-HTTLPR基因型及其与创伤事件数量在PTSD预测中的相互作用。
分析基于来自3045名参与波美拉尼亚健康研究的受试者的数据。所有参与者均使用DSM-IV结构化临床访谈的PTSD模块进行评估。对5-HTTLPR的短（S）/长（L）多态性（rs4795541）和A-G多态性（rs25531）进行基因分型。
在参与者中，1663人曾暴露于至少一次创伤事件，67人（4.0%）患上了PTSD。在经历少于三次创伤事件的人群中，携带零个、一个和两个L（A）等位基因者的PTSD终生患病率分别为2.6%、3.5%和4.3%，但在经历三次或更多创伤事件的人群中，终生患病率分别为0%、7.3%和19.6%。这一发现表明L（A）/L（A）基因型在频繁创伤方面存在累加的额外风险，这通过交互作用导致的相对额外风险（RERI）得到了证实。在等位基因分析中，RERI为3.3。因此，由于PTSD与L（A）等位基因之间的相互作用，暴露于三次或更多创伤的L（A）等位基因携带者患PTSD的优势比高出3.3倍。
发现5-HTTLPR的高表达L（A）等位基因与PTSD中的频繁创伤存在累加的基因-环境相互作用。归因比例表明，所有暴露于三次或更多创伤的L（A）等位基因携带者中，超过60%因基因型与暴露之间的相互作用而患上了PTSD。
