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Cytokine Gene Polymorphisms and Parkinson's Disease: A Meta-Analysis

Published online by Cambridge University Press:  02 December 2014

Chu Ketan ,
Zhou Xiao  and
Luo Ben-yan
Chu Ketan
Affiliation:
Department of Neurology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Zhou Xiao
Affiliation:
Department of Neurology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Luo Ben-yan*
Affiliation:
Department of Neurology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
*
Department of Neurology, First Affiliated Hospital, Zhejiang University School of Medicine, 76# Qingchun Riad, Hangzhou, 310003, China.
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Abstract

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Background:

Cytokines, which are involved in immunological responses, play important role in the development and progression of Parkinson's disease (PD). The functional polymorphisms identified in cytokine genes are thought to influence PD risk. However, the findings of studies investigating the association between cytokine gene polymorphisms and PD risk are still controversial. Therefore, we conducted a meta-analysis, in order to investigate the potential associations between cytokine gene polymorphisms and PD.

Methods:

Studies of PD and cytokine polymorphisms were identified by searches of PubMed and PDGene. Pooled analyses were performed to assess the association between cytokine gene polymorphisms and PD.

Results:

Our results indicated a positive association of TNFα -1031 CC genotype in overall analysis(CC vs. TT: OR=3.146; 95%CI: 1.631-6.070, p=0.008; CC vs. CT+TT: OR=3.187; 95%CI: 1.657-6.128, p=0.008), and an Asian subgroup, C variant(OR=1.328; 95%CI: 1.053-1.675, p=0.034) also conveyed an increased PD risk as well as CC genotype (CC vs. TT: OR=3.207; 95%CI: 1.614-6.373, p=0.004; CC vs. CT+TT: OR=3.238; 95%CI: 1.636-6.410, p=0.004). A decreased risk for PD was associated with IL-6-174C allele (OR=0.761; 95%CI: 0.641-0.903, p=0.008) and IL-1RA VNTR 2 allele(OR=0.641; 95%CI: 0.456-0.826 p=0.004). For the polymorphisms of IL-1β C[-511]T, IL-1α C[-889]T, TNFα G[-308]A, and IL-10 G[-1082]A no significant association was found between the gene polymorphisms and PD risk.

Conclusions:

Our meta-analysis suggested that gene polymorphisms of TNFα -1031, IL-6-174 and IL-1RA VNTR may be associated with PD risk. However, more large well-designed studies will be necessary to validate our findings.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 39 , Issue 1 , January 2012 , pp. 58 - 64
Copyright
Copyright © The Canadian Journal of Neurological 2012

References

1Hirsch, EC, Hunot, S.Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol. 2009; 8(4): 382–97.CrossRefGoogle ScholarPubMed
2Ogata, A, Tashiro, K, Pradhan, S.Parkinsonism due to predominant involvement of substantia nigra in Japanese encephalitis. Neurology. 2000; 55(4): 602.CrossRefGoogle ScholarPubMed
3Ling, ZD, Chang, Q, Lipton, JW, et al.Combined toxicity of prenatal bacterial endotoxin exposure and postnatal 6-hydroxydopamine in the adult rat midbrain. Neuroscience. 2004; 124(3): 619–28.Google Scholar
4Long-Smith, CM, Sullivan, AM, Nolan, YM.The influence of microglia on the pathogenesis of Parkinson’s disease. Prog Neurobiol. 2009; 89(3): 277–87.CrossRefGoogle ScholarPubMed
5Imamura, K, Hishikawa, N, Sawada, M, et al.Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains.. Acta Neuropathol. 2003; 106(6): 518–26.Google Scholar
6Mirza, B, Hadberg, H, Thomsen, P, et al.The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson’s disease. Neuroscience. 2000; 95(2): 425–32.CrossRefGoogle ScholarPubMed
7Ghosh, A, Roy, A, Liu, X, et al.Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA. 2007; 104(47): 18754–9.Google Scholar
8Wang, T, Zhang, W, Pei, Z, et al.Reactive microgliosis participates in MPP+-induced dopaminergic neurodegeneration: role of 67 kDa laminin receptor. FASEB J. 2006; 20(7): 906–15.CrossRefGoogle ScholarPubMed
9Chen, H, Zhang, SM, Hernan, MA, et al.Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol. 2003; 60(8): 1059–64.Google Scholar
10Chen, H, Jacobs, E, Schwarzschild, MA, et al.Nonsteroidal anti-inflammatory drug use and the risk for Parkinson’s disease. Ann Neurol. 2005; 58(6): 963–7.CrossRefGoogle ScholarPubMed
11Blum-Degen, D, Muller, T, Kuhn, W, et al.Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett. 1995; 202(1-2): 17–20.Google Scholar
12Mogi, M, Harada, M, Riederer, P, et al.Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett. 1994; 165(1-2): 208–10.CrossRefGoogle ScholarPubMed
13Mogi, M, Harada, M, Kondo, T, et al.Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett. 1994; 180(2): 147–50.Google Scholar
14Mogi, M, Togari, A, Kondo, T, et al.Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from parkinsonian brain. J Neural Transm. 2000; 107(3): 335–41.Google Scholar
15Gayle, DA, Ling, Z, Tong, C, et al.Lipopolysaccharide (LPS)-induced dopamine cell loss in culture: roles of tumor necrosis factor-alpha, interleukin-1beta, and nitric oxide. Brain Res Dev Brain Res. 2002; 133(1): 27–35.Google Scholar
16Nishimura, M, Mizuta, I, Mizuta, E, et al.Influence of interleukin-1beta gene polymorphisms on age-at-onset of sporadic Parkinson’s disease. Neurosci Lett. 2000; 284(1-2): 73–6.Google Scholar
17Dodel, RC, Lohmuller, F, Du, Y, et al.Apolymorphism in the intronic region of the IL-1alpha gene and the risk for Parkinson’s disease. Neurology. 2001; 56(7): 982–3.CrossRefGoogle Scholar
18McGeer, PL, Yasojima, K, McGeer, EG.Association of interleukin-1 beta polymorphisms with idiopathic Parkinson’s disease. Neurosci Lett. 2002; 326(1): 67–9.Google Scholar
19Schulte, T, Schols, L, Muller, T, et al.Polymorphisms in the interleukin-1 alpha and beta genes and the risk for Parkinson’s disease. Neurosci Lett. 2002; 326(1): 70–2.CrossRefGoogle ScholarPubMed
20Mattila, KM, Rinne, JO, Lehtimaki, T, et al.Association of an interleukin 1B gene polymorphism (-511) with Parkinson’s disease in Finnish patients. J Med Genet. 2002; 39(6): 400–2.CrossRefGoogle ScholarPubMed
21Moller, JC, Depboylu, C, Kolsch, H, et al.Lack of association between the interleukin-1 alpha (-889) polymorphism and early-onset Parkinson’s disease. Neurosci Lett. 2004; 359(3): 195–7.CrossRefGoogle ScholarPubMed
22Wu, YR, Chen, CM, Hwang, JC, et al.Interleukin-1 alpha polymorphism has influence on late-onset sporadic Parkinson’s disease in Taiwan. J Neural Transm. 2007; 114(9): 1173–7.CrossRefGoogle ScholarPubMed
23Zhou, YT, Yang, JF, Zhang, YL, et al.Protective role of interlekin-1 alpha gene polymorphism in Chinese Han population with sporadic Parkinson’s disease. Neurosci Lett. 2008; 445(1): 23–5.CrossRefGoogle ScholarPubMed
24Infante, J, Garcia-Gorostiaga, I, Sanchez-Juan, P, et al.Inflammation-related genes and the risk of Parkinson’s disease: a multilocus approach. Eur J Neurol. 2008; 15(4): 431–3.Google Scholar
25Arman, A, Isik, N, Coker, A, et al.Association between sporadic Parkinson disease and interleukin-1beta -511 gene polymorphisms in the Turkish population. Eur Cytokine Netw. 21(2): 116–121.Google Scholar
26Nishimura, M, Kuno, S, Kaji, R, et al.Glutathione-S-transferase-1 and interleukin-1beta gene polymorphisms in Japanese patients with Parkinson’s disease. Mov Disord. 2005; 20(7): 901–2.Google Scholar
27Wahner, AD, Sinsheimer, JS, Bronstein, JM, et al.Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease. Arch Neurol. 2007; 64(6): 836–40.Google Scholar
28Kruger, R, Hardt, C, Tschentscher, F, et al.Genetic analysis of immunomodulating factors in sporadic Parkinson’s disease. J Neural Transm. 2000; 107(5): 553–62.Google Scholar
29Nishimura, M, Mizuta, I, Mizuta, E, et al.Tumor ncrosis factor gene polymorphisms in patients with sporadic Parkinson’s disease. Neurosci Lett. 2001; 311(1): 1–4.CrossRefGoogle Scholar
30Ross, OA, O’Neill, C, Rea, IM, et al.Functional promoter region polymorphism of the proinflammatory chemokine IL-8 gene associates with Parkinson’s disease in the Irish. Hum Immunol. 2004; 65(4): 340–6.Google Scholar
31Wu, YR, Feng, IH, Lyu, RK, et al.Tumor necrosis factor-alpha promoter polymorphism is associated with the risk of Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet. 2007; 144B(3): 300–4.CrossRefGoogle ScholarPubMed
32Bialecka, M, Klodowska-Duda, G, Kurzawski, M, et al.Interleukin-10 (IL10) and tumor necrosis factor alpha (TNF) gene polymorphisms in Parkinson’s disease patients. Parkinsonism Relat Disord. 2008; 14(8): 636–40.Google Scholar
33Hakansson, A, Westberg, L, Nilsson, S, et al.Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet. 2005; 133B(1): 88–92.Google Scholar
34Hakansson, A, Westberg, L, Nilsson, S, et al.Investigation of genes coding for inflammatory components in Parkinson’s disease. Mov Disord. 2005; 20(5): 569–73.Google Scholar
35Pascale, E, Passarelli, E, Purcaro, C, et al.Lack of association between IL-1beta, TNF-alpha, and IL-10 gene polymorphisms and sporadic Parkinson’s disease in an Italian cohort. Acta Neurol Scand. 2011; 124(3):176–81.Google Scholar
36Lau, J, Ioannidis, JP, Schmid, CH.Quantitative synthesis in systematic reviews. Ann Intern Med. 1997; 127(9): 820–6.Google Scholar
37Xue, H, Lin, B, Ni, P, et al.Interleukin-1B and interleukin-1 RN polymorphisms and gastric carcinoma risk: a meta-analysis. J Gastroenterol Hepatol. 25(10): 1604–17.Google Scholar
38Egger, M, Davey Smith, G, Schneider, M, et al.Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315(7109): 629–34.Google Scholar
39Holm, S.A simple sequentially rejective multiple test procedure. Scand J Statist. 1979; 6: 65–70.Google Scholar
40Bialecka, M, Klodowska-Duda, G, Kurzawski, M, et al.Interleukin-10 gene polymorphism in Parkinson’s disease patients. Arch Med Res. 2007; 38(8): 858–63.Google Scholar
41Park, YJ, Park, H, Park, MH.TNF-alpha promoter polymorphisms and extended HLA and TNF-alpha haplotypes in Koreans based on 100 families. Tissue Antigens. 2004; 63(1): 75–9.Google Scholar
42Higuchi, T, Seki, N, Kamizono, S, et al.Polymorphism of the 5’-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese. Tissue Antigens. 1998; 51(6): 605–12.Google Scholar
43Li, N, Zhou, Z, Liu, X, et al.Association of tumour necrosis factor alpha (TNF-alpha) polymorphisms with Graves’ disease: A meta-analysis. Clin Biochem. 2008; 41(10-11): 881–6.Google Scholar
44Touma, Z, Farra, C, Hamdan, A, et al.TNF polymorphisms in patients with Behcet disease: a meta-analysis. Arch Med Res. 41(2):142–6.Google Scholar
45Heyser, CJ, Masliah, E, Samimi, A, et al.Progressive decline in avoidance learning paralleled by inflammatory neuro-degeneration in transgenic mice expressing interleukin 6 in the brain. Proc Natl Acad Sci USA. 1997; 94(4): 1500–5.CrossRefGoogle Scholar
46Ladenheim, B, Krasnova, IN, Deng, X, et al.Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6. Mol Pharmacol. 2000; 58(6): 1247–56.Google Scholar
47Danis, VA, Millington, M, Hyland, VJ, et al.Cytokine production by normal human monocytes: inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin Exp Immunol. 1995; 99(2): 303–10.Google Scholar
48Serdaroglu, G, Alpman, A, Tosun, A, et al.Febrile seizures: interleukin 1beta and interleukin-1 receptor antagonist polymorphisms. Pediatr Neurol. 2009; 40(2): 113–6.Google Scholar
49Chou, IC, Lin, WD, Wang, CH, et al.Interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10, and tumor necrosis factor alpha gene polymorphisms in patients with febrile seizures. J Clin Lab Anal. 24(3): 154–9.Google Scholar
50Trikalinos, TA, Salanti, G, Khoury, MJ, et al.Impact of violations and deviations in Hardy-Weinberg equilibrium on postulated gene-disease associations. Am J Epidemiol. 2006; 163(4): 300–9.Google Scholar
51Thakkinstian, A, Dmitrienko, S, Gerbase-Delima, M, et al.Association between cytokine gene polymorphisms and outcomes in renal transplantation: a meta-analysis of individual patient data. Nephrol Dial Transplant. 2008; 23(9): 3017–23.Google Scholar