Top

Published in:

01-11-2019 | Parkinson's Disease | Neurology and Preclinical Neurological Studies - Original Article

Association of polymorphisms in the MCP-1 and CCR2 genes with the risk of Parkinson’s disease

Authors: Yan Wang, Minhua Zhou, Yong Wang, Deqi Jiang, Xun Deng

Published in: Journal of Neural Transmission | Issue 11/2019

Abstract

Studies investigating the impact of polymorphisms on monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor (CCR2) on the susceptibility of Parkinson’s disease (PD) have reported inconsistent results. Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two gene polymorphisms and PD risk. We performed a meta-analysis of five eligible studies to summarize the data describing the association between PD risk and polymorphisms in MCP-1 A2518G and CCR2 V64I. The association was evaluated by calculating the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). A significant increased risk of PD was observed in the MCP-1 A2518G polymorphism in allele model (G vs. A: OR 1.12, 95% CI 1.01–1.25, p = 0.03). The dominant model of MCP-1 A2518G genotype showed no significant association with PD risk, while the risk tendency was increased (AG + GG vs. AA: OR 1.20, 95% CI 1.00–1.42, p = 0.05). In addition, CCR2 V64I polymorphism showed no significant association with PD risk (I vs. V: OR 0.33, 95% CI 0.06–1.92, p = 0.22; VI + II vs. VV: OR 1.00, 95% CI 0.83–1.21, p = 0.99). In subgroup analysis by ethnicity, no significant difference was found in both Caucasians and Asians between CCR2 V64I polymorphism and PD risk, while a significant statistical association was identified in Asians between MCP-1 A2518G polymorphism and PD risk. When the data were stratified by study area, the increased risk of PD was observed only in studies conducted in China. In summary, the present meta-analysis suggests that genetic polymorphisms of MCP-1 A2518G may influence the susceptibility of PD in Asian countries, especially in China. However, CCR2 V64I polymorphism is not correlated with PD risk. The results should be interpreted with caution due to limited sample and heterogeneity. Large scale and well-designed studies are needed to validate our findings.

Available only for authorised users

Amor S, Peferoen LA, Vogel DY, Breur M, van der Valk P, Baker D, van Noort JM (2014) Inflammation in neurodegenerative diseases—an update. Immunology 142(2):151–166CrossRef

Bajetto A, Bonavia R, Barbero S, Florio T, Schettini G (2001) Chemokines and their receptors in the central nervous system. Front Neuroendocrinol 22(3):147–184CrossRef

Bose S, Cho J (2013) Role of chemokine CCL2 and its receptor CCR3 in neurodegenerative diseases. Arch Pharm Res 36(9):1039–1050CrossRef

Conductier G, Blondeau N, Guyon A, Nahon JL, Rovere C (2010) The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J Neuroimmunol 224(1–2):93–100CrossRef

Gao L, Tang H, Nie K, Wang L, Zhao J, Gan R, Huang J, Feng S, Zhu R, Duan Z, Zhang Y, Zhao X, Zhang Y, Wang L (2015) MCP-1 and CCR5 gene polymorphisms in Parkinson’s disease in a Han Chinese cohort. Neurol Sci 36(4):571–576CrossRef

Grozdanov V, Bliederhaeuser C, Ruf WP, Roth V, Fundel-Clemens K, Zondler L, Brenner D, Martin-Villalba A, Hengerer B, Kassubek J, Ludolph AC, Weishaupt JH, Danzer KM (2014) Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients. Acta Neuropathol 128(5):651–663CrossRef

Gualtierotti R, Guarnaccia L, Beretta M, Navone SE, Campanella R, Riboni L, Rampini P, Marfia G (2017) Modulation of neuroinflammation in the central nervous system: role of chemokines and sphingolipids. Adv Ther 34(2):396–420CrossRef

Huerta C, Alvarez V, Mata IF, Coto E, Ribacoba R, Martinez C, Blazquez M, Guisasola LM, Salvador C, Lahoz CH, Pena J (2004) Chemokines (RANTES and MCP-1) and chemokine-receptors (CCR8 and CCR8) gene polymorphisms in Alzheimer’s and Parkinson’s disease. Neurosci Lett 370(2–3):151–154CrossRef

Kannarkat GT, Boss JM, Tansey MG (2013) The role of innate and adaptive immunity in Parkinson’s disease. J Parkinsons Dis 3(4):493–514PubMedPubMedCentral

Lindqvist D, Hall S, Surova Y, Nielsen HM, Janelidze S, Brundin L, Hansson O (2013) Cerebrospinal fluid inflammatory markers in Parkinson’s disease—associations with depression, fatigue, and cognitive impairment. Brain Behav Immun 33:183–189CrossRef

Meissner WG, Frasier M, Gasser T, Goetz CG, Lozano A, Piccini P, Obeso JA, Rascol O, Schapira A, Voon V, Weiner DM, Tison F, Bezard E (2011) Priorities in Parkinson’s disease research. Nat Rev Drug Discov 10(5):377–393CrossRef

Nishimura M, Kuno S, Mizuta I, Ohta M, Maruyama H, Kaji R, Kawakami H (2003) Influence of monocyte chemoattractant protein 1 gene polymorphism on age at onset of sporadic Parkinson’s disease. Mov Disord 18(8):953–955CrossRef

Reale M, Iarlori C, Thomas A, Gambi D, Perfetti B, Di Nicola M, Onofrj M (2009) Peripheral cytokines profile in Parkinson’s disease. Brain Behav Immun 23(1):55–63CrossRef

Rovin BH, Lu L, Saxena R (1999) A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun 259(2):344–348CrossRef

Sahin-Calapoglu N, Demirci S, Calapoglu M, Yasar B (2016) A case–control association study of RANTES (−28C>G) polymorphism as a risk factor for Parkinson’s disease in Isparta, Turkey. Parkinsons Dis 2016:5042604PubMedPubMedCentral

Schapira AH, Jenner P (2011) Etiology and pathogenesis of Parkinson’s disease. Mov Disord 26(6):1049–1055CrossRef

Shen R, Lin S, He L, Zhu X, Zhou Z, Chen S, Wang Y, Ding J (2019) Association of two polymorphisms in CCL2 with Parkinson’s disease: a case–control study. Front Neurol 10:35CrossRef

Sozzani S, Zhou D, Locati M, Rieppi M, Proost P, Magazin M, Vita N, van Damme J, Mantovani A (1994) Receptors and transduction pathways for monocyte chemotactic protein-2 and monocyte chemotactic protein-3. Similarities and differences with MCP-1. J Immunol 152(7):3615–3622PubMed

Stojkovska I, Wagner BM, Morrison BE (2015) Parkinson’s disease and enhanced inflammatory response. Exp Biol Med (Maywood) 240(11):1387–1395CrossRef

Tansey MG, McCoy MK, Frank-Cannon TC (2007) Neuroinflammatory mechanisms in Parkinson’s disease: potential environmental triggers, pathways, and targets for early therapeutic intervention. Exp Neurol 208(1):1–25CrossRef

Title: Association of polymorphisms in the MCP-1 and CCR2 genes with the risk of Parkinson’s disease
Authors: Yan Wang
Minhua Zhou
Yong Wang
Deqi Jiang
Xun Deng
Publication date: 01-11-2019
Publisher: Springer Vienna
Keyword: Parkinson's Disease
Published in: Journal of Neural Transmission / Issue 11/2019
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-019-02072-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Association of polymorphisms in the MCP-1 and CCR2 genes with the risk of Parkinson’s disease

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 11/2019

“New methods of assessing autonomic disorders in Parkinson disease patients: skin-galvanic reaction”

FGF2 and dual agonist of NCAM and FGF receptor 1, Enreptin, rescue neurite outgrowth loss in hippocampal neurons expressing mutated huntingtin proteins

Early detection of cognitive impairment in Parkinson’s disease with the use of the Wisconsin Card Sorting Test: correlations with Montreal Cognitive Assessment and smell identification test

Subthalamic nucleus deep brain stimulation improves dyskinesias in Parkinson’s disease beyond levodopa reduction

Late-onset Niemann–Pick disease type C overlapping with frontotemporal dementia syndromes: a case report

Salivary alpha-synuclein as a biomarker for Parkinson’s disease: a systematic review