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TPH1 和 TPH2 基因单核苷酸多态性与抑郁障碍的关联。

Association between single nucleotide polymorphisms of TPH1 and TPH2 genes, and depressive disorders.

机构信息

Laboratory of Medical Genetics, Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.

Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.

出版信息

J Cell Mol Med. 2018 Mar;22(3):1778-1791. doi: 10.1111/jcmm.13459. Epub 2018 Jan 5.

Abstract

Tryptophan catabolites pathway disorders are observed in patients with depression. Moreover, single nucleotide polymorphisms of tryptophan hydroxylase genes may modulate the risk of depression occurrence. The objective of our study was to confirm the association between the presence of polymorphic variants of TPH1 and TPH2 genes, and the development of depressive disorders. Six polymorphisms were selected: c.804-7C>A (rs10488682), c.-1668T>A (rs623580), c.803+221C>A (rs1800532), c.-173A>T (rs1799913)-TPH1, c.-1449C>A (rs7963803), and c.-844G>T (rs4570625)-TPH2. A total of 510 DNA samples (230 controls and 280 patients) were genotyped using TaqMan probes. Among the studied polymoorphisms, the G/G genotype and G allele of c.804-7C>A-TPH1, the T/T homozygote of c.803+221C>A-TPH1, the A/A genotype and A allele of c.1668T>A-TPH1, the G/G homozygote and G allele of c.-844G>T-TPH2, and the C/A heterozygote and A allele of c.-1449C>A-TPH2 were associated with the occurrence of depression. However, the T/T homozygote of c.-1668T>A-TPH1, the G/T heterozygote and T allele of c.-844G>T-TPH2, and the C/C homozygote and C allele of c.-1449C>A-TPH2 decreased the risk of development of depressive disorders. Each of the studied polymorphisms modulated the risk of depression for selected genotypes and alleles. These results support the hypothesis regarding the involvement of the pathway in the pathogenesis of depression.

摘要

色氨酸分解代谢途径障碍在抑郁症患者中观察到。此外,色氨酸羟化酶基因的单核苷酸多态性可能调节抑郁症发生的风险。我们研究的目的是确认 TPH1 和 TPH2 基因的多态性变异的存在与抑郁障碍的发展之间的关联。选择了六个多态性:c.804-7C>A(rs10488682)、c.-1668T>A(rs623580)、c.803+221C>A(rs1800532)、c.-173A>T(rs1799913)-TPH1、c.-1449C>A(rs7963803)和 c.-844G>T(rs4570625)-TPH2。使用 TaqMan 探针对总共 510 个 DNA 样本(230 个对照和 280 个患者)进行了基因分型。在所研究的多态性中,c.804-7C>A-TPH1 的 G/G 基因型和 G 等位基因、c.803+221C>A-TPH1 的 T/T 纯合子、c.1668T>A-TPH1 的 A/A 基因型和 A 等位基因、c.-844G>T-TPH2 的 G/G 纯合子和 G 等位基因,以及 c.-1449C>A-TPH2 的 C/A 杂合子和 A 等位基因与抑郁症的发生有关。然而,c.1668T>A-TPH1 的 T/T 纯合子、c.-844G>T-TPH2 的 G/T 杂合子和 T 等位基因以及 c.-1449C>A-TPH2 的 C/C 纯合子和 C 等位基因降低了抑郁障碍发展的风险。所研究的每种多态性都调节了所选基因型和等位基因的抑郁症风险。这些结果支持了该途径参与抑郁症发病机制的假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea14/5824396/017d57674196/JCMM-22-1778-g001.jpg

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