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韩国人群中 Unc-51 样自噬激活激酶 2 基因多态性与精神分裂症的关联。

Association between Unc-51-like autophagy activating kinase 2 gene polymorphisms and schizophrenia in the Korean population.

机构信息

Department of Neuropsychiatry, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.

Department of Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea.

出版信息

Medicine (Baltimore). 2022 Feb 4;101(5):e28745. doi: 10.1097/MD.0000000000028745.

Abstract

Accumulating evidence indicates that the autophagy process is involved in the pathogenesis of schizophrenia. Autophagy plays a fundamental role in neuronal survival and function, and autophagy-related genes have been suggested to be associated with the pathogenesis of schizophrenia. The Unc-51-like autophagy activating kinase 2 (ULK2) gene has been implicated in autophagy regulation; therefore, we hypothesized that ULK2 polymorphisms may be associated with schizophrenia susceptibility.This study explored the association between polymorphisms of ULK2 and schizophrenia.Two single nucleotide polymorphisms (SNPs) (rs55730189 and rs150122) of ULK2 were genotyped in 279 patients with schizophrenia and 403 healthy individuals using Fluidigm SNPtype assays. We analyzed the genotype distribution of 2 SNPs and haplotypes between patients with schizophrenia and control subjects.The T allele frequency of rs55730189 showed a significant association between patients with schizophrenia and control subjects (P = .003). Genotype frequencies of rs55710189 were found to be significantly different between patients with schizophrenia and control subjects (odds ratio = 6.89, 95% confidence interval = 1.91-24.90, P < .001 in the dominant model [C/T + T/T vs C/C], OR = 6.50, 95% confidence interval = 1.83-23.01, P < .001 in the log-additive model (C/T vs T/T vs C/C)]. In haplotype analysis, the TT haplotype for these 2 SNPs was significantly associated with schizophrenia (P < .001, χ2 = 12.231).Our findings suggest that specific ULK2 polymorphisms may be associated with susceptibility to schizophrenia in the Korean population.

摘要

越来越多的证据表明,自噬过程参与了精神分裂症的发病机制。自噬在神经元的存活和功能中起着至关重要的作用,并且已经有研究表明与精神分裂症发病机制相关的自噬相关基因。非典型卷曲相关蛋白 51 样自噬激活激酶 2(ULK2)基因参与自噬的调节;因此,我们假设 ULK2 多态性可能与精神分裂症易感性有关。本研究探讨了 ULK2 多态性与精神分裂症之间的关联。使用 Fluidigm SNPtype 分析方法,对 279 例精神分裂症患者和 403 例健康对照者的 ULK2 两个单核苷酸多态性(SNP)(rs55730189 和 rs150122)进行基因分型。我们分析了 SNP 与精神分裂症患者和对照组之间的基因型分布和单倍型。rs55730189 的 T 等位基因频率在精神分裂症患者和对照组之间存在显著差异(P=0.003)。rs55730189 的基因型频率在精神分裂症患者和对照组之间存在显著差异(优势比=6.89,95%置信区间=1.91-24.90,P<0.001,显性模型[C/T+T/T 与 C/C];优势比=6.50,95%置信区间=1.83-23.01,P<0.001,对数相加模型(C/T 与 T/T 与 C/C))。在单倍型分析中,这两个 SNP 的 TT 单倍型与精神分裂症显著相关(P<0.001,χ2=12.231)。我们的研究结果表明,特定的 ULK2 多态性可能与韩国人群的精神分裂症易感性有关。

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