Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
Eur Psychiatry. 2018 Aug;52:95-103. doi: 10.1016/j.eurpsy.2018.05.001. Epub 2018 May 25.
Numerous data suggests that the disorders of tryptophan catabolites (TRYCATs) pathway, including a decreased level of tryptophan or evaluated concentration of harmful TRYCATs -kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, 3-hydroxytryptophan - may cause the occurrence of DD symptoms. In this work, we assessed the relationship between single-nucleotide polymorphisms (SNPs) of KAT1, KAT2 and IDO1 gene encoding, and the risk of depression development. Our study was performed on the DNA isolated from peripheral blood of 281 depressed patients and 236 controls. We genotyped, by using TaqMan probes, four polymorphisms: c.*456G > A of KAT1 (rs10988134), c.975-7T > C of AADAT (rs1480544), c.-1849C > A (rs3824259) and c.-1493G > C(rs10089084)of IDO1. We found that only the A/A genotype of c.*456G > A - KAT1 (rs10988134) increased the risk of depression occurrence. Interestingly, when we stratified the study group according to gender, this relationship was present only in male population. However, a gene-gene analysis revealed a link between the T/T-C/C genotype of c.975-7T > C - AADAT (rs1480544)or c.-1493G > C - IDO1 (rs10089084) and C/C-C/A genotype of c.975-7T > C - AADAT (rs1480544)and c. -1849C > A - IDO1 (rs3824259) and the disease. Moreover, we found, that the c.975-7T > C - AADAT and c. *456G > A KAT1 (rs10988134) polymorphisms may modulate the effectiveness of selective serotonin reuptake inhibitors therapy. Concluding, our results confirm the hypothesis formulated in our recently published article that the SNPs of genes involved in TRYCATs pathway may modulate the risk of depression. This provides some further evidence that the pathway plays the crucial role in development of the disease.
大量数据表明，色氨酸分解代谢产物（TRYCATs）途径的紊乱，包括色氨酸水平降低或有害 TRYCATs 的评估浓度-犬尿氨酸、喹啉酸、3-羟基邻氨基苯甲酸、3-羟基色氨酸-可能导致 DD 症状的发生。在这项工作中，我们评估了编码 KAT1、KAT2 和 IDO1 基因的单核苷酸多态性（SNP）与抑郁症发展风险之间的关系。我们的研究是在 281 名抑郁症患者和 236 名对照者外周血分离的 DNA 上进行的。我们使用 TaqMan 探针对四种多态性进行了基因分型：KAT1 的 c.*456G > A（rs10988134）、AADAT 的 c.975-7T > C（rs1480544）、c.-1849C > A（rs3824259）和 IDO1 的 c.-1493G > C（rs10089084）。我们发现，只有 KAT1（rs10988134）c.*456G > A 的 A/A 基因型增加了抑郁症发生的风险。有趣的是，当我们根据性别对研究组进行分层时，这种关系仅存在于男性人群中。然而，基因-基因分析显示，c.975-7T > C-AADAT（rs1480544）或 c.-1493G > C-IDO1（rs10089084）的 T/T-C/C 基因型与 c.975-7T > C-AADAT（rs1480544）和 c.-1849C > A-IDO1（rs3824259）的 C/C-C/A 基因型之间存在关联。此外，我们发现，c.975-7T > C-AADAT 和 c.*456G > A KAT1（rs10988134）多态性可能调节选择性 5-羟色胺再摄取抑制剂治疗的效果。总之，我们的结果证实了我们最近发表的文章中提出的假设，即参与 TRYCATs 途径的基因的 SNP 可能调节抑郁症的风险。这为该途径在疾病发展中起着关键作用提供了一些进一步的证据。
