吲哚胺 2,3-双加氧酶 1 的单核苷酸多态性影响帕金森病的发病年龄。

Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase 1 Influenced the Age Onset of Parkinson's Disease.

机构信息

ELKH-SZTE Neuroscience Research Group, Danube Neuroscience Research Laboratory, Eötvös Loránd Research Network, University of Szeged (ELKH-SZTE), Danube Neuroscience Research Laboratory, H-6725 Szeged, Hungary.

Institute of Biophysics, Biological Research Centre, Eötvös Loránd Research Network (ELKH), H-6726 Szeged, Hungary.

出版信息

Front Biosci (Landmark Ed). 2022 Sep 27;27(9):265. doi: 10.31083/j.fbl2709265.

DOI:10.31083/j.fbl2709265

PMID:36224022

Abstract

BACKGROUND

Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson's disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. More and more single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known about the impact of genetic variations of the IDO on the pathogenesis of PD.

METHODS

SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls.

RESULTS

No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers.

CONCLUSIONS

The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

摘要

背景

早期的研究报道了色氨酸（TRP）代谢中的犬尿氨酸（KYN）途径在帕金森病（PD）中的改变。观察到第一限速酶吲哚胺 2,3-双加氧酶（IDO）和色氨酸双加氧酶上调，导致 PD 患者的血清和脑脊液样本中的 KYN/TRP 比值升高。在 PD 人群中已经鉴定出越来越多的单核苷酸多态性（SNP）。然而，关于 IDO 的遗传变异对 PD 发病机制的影响知之甚少。

方法

通过荧光标记 TaqMan 探针的等位基因鉴别检测法对 IDO1 的 SNP 进行分析，并根据 PD 发病年龄进行亚组分析。对 105 名无合并症的 PD 患者的框移变体 rs34155785、内含子变体 rs7820268 和启动子区域变体 rs9657182 SNP 进行分析，并与 129 名健康对照进行比较。