Karanović Jelena, Ivković Maja, Jovanović Vladimir M, Šviković Saša, Pantović-Stefanović Maja, Brkušanin Miloš, Damjanović Aleksandar, Brajušković Goran, Savić-Pavićević Dušanka
Center for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Studentski trg 16, PO box 43, Belgrade, 11000, Serbia.
Clinic for Psychiatry, Clinical Centre of Serbia, Pasterova 2, Belgrade, 11000, Serbia.
J Neural Transm (Vienna). 2017 May;124(5):621-629. doi: 10.1007/s00702-017-1677-z. Epub 2017 Jan 13.
Suicidal behavior has been associated with a deficient serotonin neurotransmission which is likely a consequence of individual genetic architecture, exposure to environmental factors and interactions of those factors. We examined whether the interaction of child abuse, TPH2 (tryptophan hydroxylase 2) variant rs4290270, affecting alternative splicing and editing of TPH2 pre-mRNAs, and ADARB1 (adenosine deaminase acting on RNA B1) variants rs4819035 and rs9983925 may influence the risk for suicide attempt in psychiatric patients. TPH2 rs4290270 was genotyped in 165 suicide attempters and 188 suicide non-attempters diagnosed with major depressive disorder, bipolar disorder and schizophrenia. Genotyping data for ADARB1 variants were taken over from our previous study. Child abuse before the age of 18 years was assessed using the Early Trauma Inventory-Self Report. Generalized linear models and backward selection were applied to identify the main and interacting effects of environmental and genetic factors, including psychiatric diagnoses, patients' gender and age as covariates. Childhood general traumas were independently associated with suicide attempt. Two-way interaction between TPH2 rs4290270 and general traumas revealed that TT homozygotes with a history of general traumas had an increased risk for suicide attempt. Three-way interaction of general traumas, TPH2 rs4290270 and ADARB1 rs4819035 indicated that the highest predisposition to suicide attempt was observed in individuals who experienced general traumas and were TT homozygote for rs4290270 and TT homozygote for rs4819035. Our findings suggest that the risk for suicide attempt in psychiatric patients exposed to an adverse childhood environment may depend on TPH2 and ADARB1 variants.
自杀行为与血清素神经传递不足有关，这可能是个体遗传结构、暴露于环境因素以及这些因素相互作用的结果。我们研究了儿童期虐待、影响TPH2前体mRNA可变剪接和编辑的TPH2（色氨酸羟化酶2）变体rs4290270，以及ADARB1（作用于RNA的腺苷脱氨酶B1）变体rs4819035和rs9983925之间的相互作用是否会影响精神病患者自杀未遂的风险。对165名自杀未遂者和188名被诊断患有重度抑郁症、双相情感障碍和精神分裂症的非自杀未遂者进行了TPH2 rs4290270基因分型。ADARB1变体的基因分型数据取自我们之前的研究。使用早期创伤问卷-自我报告评估18岁之前的儿童期虐待情况。应用广义线性模型和向后选择来确定环境和遗传因素的主要和相互作用效应，包括精神病诊断、患者的性别和年龄作为协变量。儿童期的一般性创伤与自杀未遂独立相关。TPH2 rs4290270与一般性创伤之间的双向相互作用表明，有一般性创伤史的TT纯合子自杀未遂风险增加。一般性创伤、TPH2 rs4290270和ADARB1 rs4819035的三向相互作用表明，在经历一般性创伤且rs4290270为TT纯合子和rs4819035为TT纯合子的个体中，自杀未遂的易感性最高。我们的研究结果表明，暴露于不良童年环境的精神病患者自杀未遂的风险可能取决于TPH2和ADARB1变体。
