Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder
Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder
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DOI：
10.1111/j.1600-079x.2010.00754.x
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发表时间：
2010-05-01
影响因子：
10.3
通讯作者：
Karbownik-Lewinska, Malgorzata
中科院分区：
文献类型：
--
作者：
Galecki, Piotr;Szemraj, Janusz;Karbownik-Lewinska, Malgorzata
抑郁症（DD）的特征在于血液褪黑激素浓度的紊乱。众所周知，褪黑激素参与昼夜节律的控制，包括睡眠。使用褪黑激素及其类似物已被发现是有效的抑郁症治疗。褪黑激素的合成是一个多阶段的过程，其中最后一个阶段是由乙酰5-羟色胺甲基转移酶（ASMT）催化的，该酶是已报道的褪黑激素合成的限速酶。考虑到遗传因素在抑郁症发展中的重要性，ASMT基因可能成为复发性DD患者研究的一个有趣的焦点。该研究的目的是评估ASMT基因的两个单核苷酸多态性（SNP）（rs4446909; rs5989681）以及复发性DD患者中ASMT的mRNA表达。我们对181例复发性DD患者和149例对照组进行了两种多态性基因分型。采用聚合酶链反应/限制性片段长度多态性方法进行研究。DD和健康受试者的ASMT基因的两个SNPs的基因型分布差异显着。rs4446909多态性AA基因型和rs5989681多态性GG基因型的存在与DD复发的风险较低相关。反过来，抑郁症患者的特征是ASMT mRNA表达减少。此外，ASMT转录水平在复发DD患者和健康受试者显着依赖于两个多态性的基因型分布。总之，我们的研究结果表明，ASMT基因作为复发性DD的易感基因。
Depressive disorder (DD) is characterised by disturbances in blood melatonin concentration. It is well known that melatonin is involved in the control of circadian rhythms, sleep included. The use of melatonin and its analogues has been found to be effective in depression therapy. Melatonin synthesis is a multistage process, where the last stage is catalysed by acetylserotonin methyltransferase (ASMT), the reported rate-limiting melatonin synthesis enzyme. Taking into account the significance of genetic factors in depression development, the gene for ASMT may become an interesting focus for studies in patients with recurrent DD. The goal of the study was to evaluate two single-nucleotide polymorphisms (SNPs) (rs4446909; rs5989681) of the ASMT gene, as well as mRNA expression for ASMT in recurrent DD-affected patients. We genotyped two polymorphisms in a group of 181 recurrent DD patients and in 149 control subjects. The study was performed using the polymerase chain reaction/restriction fragment length polymorphism method. The distribution of genotypes in both studied SNPs in the ASMT gene differed significantly between DD and healthy subjects. The presence of AA genotype of rs4446909 polymorphism and of GG genotype of rs5989681 polymorphism was associated with lower risk for having recurrent DD. In turn, patients with depression were characterised by reduced mRNA expression for ASMT. In addition, ASMT transcript level in both recurrent DD patients and in healthy subjects depended significantly on genotype distributions in both polymorphisms. In conclusion, our results suggest the ASMT gene as a susceptibility gene for recurrent DD.