Association of NQO1 and TNF polymorphisms with Parkinson’s disease: A meta-analysis of 15 genetic association studies

Abstract

Abstract. Parkinson's disease (PD) is a neurodegenerative movement d'isorder that affects ~2% of the population aged ≥65 years. NAD(P)H-quinone oxidoreductase 1 (NQO1) and tumor necrosis factor-α (TNF-α) are two important factors in the generation of oxidative stress in PD. The aim of the present study was to assess the association of NQO1 and tumor necrosis factor (TNF) polymorphisms with PD. A meta-analysis was performed that included data from 15 studies comprising 2,858 patients and 2,907 healthy controls. The results showed that TNF-1031 (rs1799964) was significantly associated with PD in the recessive [P=0.0005; odds ratio (OR), 3.19; 95% confidence interval (CI), 1.66-6.13] and additive models (P=0.0006; OR, 3.15; 95% CI, 1.63-3.51). However, there was no significant association in NQO1 C609T (rs1800566) and TNF-308 (rs1800629) with PD. To the best of our knowledge, the present study is the first meta-analysis of NQO1 and TNF polymorphisms with PD demonstrating that TNF-1031 polymorphism may be a risk factor for PD under either the recessive or additive models. However, the meta-analyses did not support the involvement of NQO1 C609T and TNF-308 in the risk of PD.

Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson’s disease

“…In this study, we evaluated the effect of selected SNPs from inflammation and oxidative stress pathways on the risk for PD and AEs occurrence due to dopaminergic treatment of PD. Several studies evaluating the effect of genetic polymorphisms or alterations in proteins’ functions in the inflammation- and oxidative stress-related pathways on the PD risk and pathogenesis have already been performed [31, 32, 34–39]. However, no studies evaluating genetic variability in these pathways affecting the occurrence of AEs of dopaminergic treatment have been conducted to date.…”

“…Also TNF-α rs1800629 has been associated with the disease risk [31], but later studies did not confirm the result [32, 33]. Moreover, two other TNF-α SNPs [34, 35] and IL6 rs1800795 [36] showed the same association. Bridge between inflammatory processes and ROS/RNS stress may be presented by NOS1 .…”

Inflammation-related gene polymorphisms associated with Parkinson’s disease: an updated meta-analysis

“…The role of TNFα -1031 T/C and -308 G/A (rs1800629) in PD was previously evaluated [22,23]. Here, we evaluated two additional TNFα polymorphisms; (TNFα -863 C/A and TNFα -857 C/T) [8,38].…”

“…To date, it is unclear whether these polymorphisms correlate with PD development and progression, as several studies are equivocal in this regard. Previous meta-analyses have been investigated associations between inflammation and PD risk [1,22,23]; however, these studies focused on cytokine polymorphisms, rather than chemokines and their receptors. Therefore, we provide an updated comprehensive meta-analysis, summarizing the latest studies evaluating associations between inflammation-related gene polymorphisms and PD.…”

Clinically Useful Biomarkers for Parkinson’s Disease

“…The genetic factors SIPA1L2, INPP5F, MIR4697, GCH1, VPS13C and DDRGK1 are involved in the onset of PD [10]. In a recent meta-analysis studies reported that TNF-1031 polymorphism is a possible risk factor for PD [11]. The roles of the genes parkin, DJ-1, PINK-1 and LRRK2 are not clear in the progression of PD [12].…”