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

Abstract

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. An increasing number of single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. 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. 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. 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.

The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson’s Disorder and Therapeutic Implications

“…The three variants of 105 PD patients with no comorbidities: intronic variant rs7820268, frame shifts variant rs34155785, and promoter region variant rs9657182, were evaluated and compared to 129 healthy control subjects. However, the A alleles of rs7820268 SNP or rs9657182 SNP carriers were found to aid the late onset of disease in PD patients, as compared to non-carriers, as reported by the subgroup analysis [69]. This investigation revealed the impact of SNPs of IDO1 on the age onset of PD and the function of SNP genotypes as a risk biomarker of PD [69].…”

“…However, the A alleles of rs7820268 SNP or rs9657182 SNP carriers were found to aid the late onset of disease in PD patients, as compared to non-carriers, as reported by the subgroup analysis [69]. This investigation revealed the impact of SNPs of IDO1 on the age onset of PD and the function of SNP genotypes as a risk biomarker of PD [69].…”

“…The serum and CSF samples of PD patients were reported to exhibit enhanced ration of KYN to TRP, as the result of elevated IDO and TDO levels. The PD population has been recognized to constitute elevated number of single nucleotide polymorphisms (SNPs); however, it is still unclear if the IDO-associated genetic disturbances lead to KYN metabolism impairment and PD [69]. Allelic discrimination assay was used to perform SNP analysis of IDO1, along with fluorescently labelled TaqMan probes.…”

“…Certain endogenous oxidative and anti-oxidative KP metabolites are also significant in this regard [120][121][122][123], such as 3-HK (oxidative) and KYNA (anti-oxidative), which were found to be related to the depressive symptoms in stroke patients [118,[124][125][126], where KYNA induced anti-depressant action in animal models of depression [127][128][129][130][131]. The onset age of neurodegeneration is regulated by IDO-1, which is related to depressive impact and inflammation [69,[132][133][134].…”

Co-Players in Chronic Pain: Neuroinflammation and the Tryptophan-Kynurenine Metabolic Pathway

“…Furthermore, the immunomodulators are known to trigger the shift of acute inflammatory status toward tolerogenic and chronic inflammation, perpetuating lowgrade inflammation [35]. KYN is synthesized from TRP by the tryptophan 2,3-dioxygenase (TDO) in the liver and the indoleamine 2, 3-oxygenase (IDO) in the brain and the immune system, which are induced by cortisol, and IFN-α, IFN-γ, and TNF-α, respectively [36]. Anthranilic acid (AA), 3-hydroxykynurenine (3-HK), or kynurenic acid (KYNA) are produced from KYN by the kynureninase, the KYN-3-monooxygenase (KMO), the KYN aminotransferases (KATs), respectively.…”