ABB  Vol.5 No.2 , January 2014
Association of four GSTs gene polymorphisms with Parkinson disease: A meta-analysis

Parkinson disease (PD) is a neurological disorder with huge destruction to human body, which affects approximately 2% of the population aged 65 years or older. As antioxidants in the stress defence systems, glutathione S-transferases (GSTs) are dimeric cytosolic enzymes with an important role in the pathogenesis of PD. The aim of this study was to evaluate the association between the polymorphisms of GST genes and PD. Meta-analyses were conducted from 17 studies (38 stages) among 3419 cases and 5686 controls between four polymorphisms (GSTT1 deletion polymorphism; GSTM1 deletion polymorphism; GSTP1-104: rs1695; GSTP1-114: rs1799811) and PD. There is no significant association between the four GST gene variants and PD. A further subgroup study by ethnicity observed a risky role of GSTM1 deletion polymorphism with PD in Europeans (p = 0.013, OR = 1.126, 95% CI = 1.025-1.236), and a protective role of GSTM1 deletion polymorphism with PD in Latin Americans (p = 0.032, OR = 0.750, 95% CI = 0.577-0.975). Our meta-analysis suggested that GSTM1 deletion polymorphism increased the risk of PD in Europeans, but reduced the risk of PD in Latin Americans. Future large-scale studies might be needed to confirm the ethnic difference of GSTM1 deletion polymorphism, and to check whether there was significant association of PD for other GST genetic polymorphisms.

Cite this paper
Dai, D. , Wang, Y. , Wang, L. , Li, J. , Zhou, H. , Ma, Q. , Zhou, X. , Pan, J. , Pan, G. , Chen, C. , Xu, L. , Ru, P. , Wang, H. , Zhu, S. , Lv, Y. , Xu, L. , Ye, M. and Duan, S. (2014) Association of four GSTs gene polymorphisms with Parkinson disease: A meta-analysis. Advances in Bioscience and Biotechnology, 5, 100-107. doi: 10.4236/abb.2014.52014.
[1]   Elbaz, A., Bower, J.H., Maraganore, D.M., McDonnell, S.K., Peterson, B.J., Ahlskog, J.E., et al., (2002) Risk tables for parkinsonism and Parkinson’s disease. Journal of Clinical Epidemiology, 55, 25-31.

[2]   Dauer, W. and Przedborski, S. (2003) Parkinson’s disease: Mechanisms and models. Neuron, 39, 889-909.

[3]   Mylius, V., Engau, I., Teepker, M., Stiasny-Kolster, K., Schepelmann, K., Oertel, W.H., et al., (2009) Pain sensitivity and descending inhibition of pain in Parkinson's disease. Journal of Neurology, Neurosurgery & Psychiatry, 80, 24-28.

[4]   Grachev, I.D. (2013) Dopamine transporter imaging with [123I]FP-CIT (DaTSCAN) in Parkinson’s disease with depressive symptoms: A biological marker for causal relationships? Journal of Neurology, Neurosurgery & Psychiatry, 2013.

[5]   Blonder, L.X., Slevin, J.T., Kryscio, R.J., Martin, C.A., Andersen, A.H., Smith, C.D., et al. (2013) Dopaminergic modulation of memory and affective processing in Parkinson depression. Psychiatry Research, 2013.

[6]   Lee, J.Y., Kim, J.M., Ahn, J., Kim, H.J., Jeon, B.S. and Kim, T.W. (2013) Retinal nerve fiber layer thickness and visual hallucinations in Parkinson’s Disease. Movement Disorders, 2013.

[7]   Aarsland, D., Zaccai, J. and Brayne, C. (2005) A systematic review of prevalence studies of dementia in Parkinson’s disease. Movement Disorder, 20, 1255-1263.

[8]   Gan, E.C., Lau, D.P. and Cheah, K.L. (2010) Stridor in Parkinson’s disease: A case of “dry drowning”? The Journal of Laryngology & Otology, 124, 668-673.

[9]   Klebe, S., Golmard, J.L., Nalls, M.A., Saad, M., Singleton, A.B., Bras, J.M., et al. (2013) The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson’s disease with a sexual dimorphism. Journal of Neurology, Neurosurgery & Psychiatry, 84, 666-673.

[10]   Rode, J., Bentley, A. and Parkinson, C. (1990) Paraganglial cells of urinary bladder and prostate: Potential diagnostic problem. Journal of Clinical Pathology, 43, 13-16.

[11]   Najafi, M.R., Chitsaz, A., Askarian, Z. and Najafi, M.A. (2013) Quality of sleep in patients with Parkinson’s disease. International Journal of Preventive Medicine, 4, S229-S233.

[12]   Horvath, J., Burkhard, P.R., Bouras, C. and Kovari, E. (2013) Etiologies of Parkinsonism in a century-long autopsy-based cohort. Brain Pathology, 23, 28-33.

[13]   Olanow, C.W. and Tatton, W.G. (1999) Etiology and pathogenesis of Parkinson’s disease. Annual Review of Neuroscience, 22, 123-144.

[14]   Wirdefeldt, K., Adami, H.O., Cole, P., Trichopoulos, D. and Mandel, J. (2011) Epidemiology and etiology of Parkinson’s disease: A review of the evidence. European Journal of Epidemiology, 26, S1-S58.

[15]   Vaglini, F., Viaggi, C., Piro, V., Pardini, C., Gerace, C., Scarselli, M., et al. (2013) Acetaldehyde and parkinsonism: Role of CYP450 2E1. Frontiers in Behavioral Neuroscience, 7, 71.

[16]   Lill, C.M., Roehr, J.T., McQueen, M.B., Kavvoura, F.K., Bagade, S., Schjeide, B.M., et al. (2012) Comprehensive research synopsis and systematic meta-analyses in Parkinson’s disease genetics: The PDGene database. PLoS Genet, 8, e1002548.

[17]   McInerney-Leo, A., Hadley, D.W., Gwinn-Hardy, K. and Hardy, J. (2005) Genetic testing in Parkinson’s disease. Movement Disorders, 20, 1-10.

[18]   Bekris, L.M., Mata, I.F. and Zabetian, C.P. (2010) The genetics of Parkinson disease. Journal of Geriatric Psychiatry and Neurology, 23, 228-242.

[19]   Travers, M.E., Mackay, D.J., Dekker Nitert, M., Morris, A.P., Lindgren, C.M., Berry, A., et al. (2013) Insights into the molecular mechanism for type 2 diabetes susceptibility at the KCNQ1 locus from temporal changes in imprinting status in human islets. Diabetes, 62, 987-992.

[20]   Ritz, B., Ascherio, A., Checkoway, H., Marder, K.S., Nelson, L.M., Rocca, W.A., et al. (2007) Pooled analysis of tobacco use and risk of Parkinson disease. Archives of Neurology, 64, 990-997.

[21]   Priyadarshi, A., Khuder, S.A., Schaub, E.A. and Shrivastava, S. (2000) A meta-analysis of Parkinson’s disease and exposure to pesticides. Neurotoxicology, 21, 435-440.

[22]   Stroombergen, M.C. and Waring, R.H. (1999) Determination of glutathione S-transferase mu and theta polymorphisms in neurological disease. Human & Experimental Toxicology, 18, 141-145.

[23]   Menegon, A., Board, P.G., Blackburn, A.C., Mellick, G.D. and Le Couteur, D.G. (1998) Parkinson’s disease, pesticides, and glutathione transferase polymorphisms. Lancet, 352, 1344-1346.

[24]   Rahbar, A., Kempkes, M., Muller, T., Reich, S., Welter, F.L., Meves, S., et al. (2000) Glutathione S-transferase polymorphism in Parkinson’s disease. Journal of Neural Transmission, 107, 331-334.

[25]   Ahmadi, A., Fredrikson, M., Jerregard, H., Akerback, A., Fall, P.A., Rannug, A., et al. (2000) GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset. Biochemical and Biophysical Research Communications, 269, 676-680.

[26]   Kelada, S.N., Stapleton, P.L., Farin, F.M., Bammler, T.K., Eaton, D.L., Smith-Weller, T., et al. (2003) Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson’s disease. Neuroscience Letters, 337, 5-8.

[27]   Dick, F.D., De Palma, G., Ahmadi, A., Osborne, A., Scott, N.W., Prescott, G.J., et al. (2007) Gene-environment interactions in parkinsonism and Parkinson’s disease: The Geoparkinson study. Occupational and Environmental Medicine, 64, 673-680.

[28]   Wahner, A.D., Glatt, C.E., Bronstein, J.M. and Ritz, B. (2007) Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson’s disease. Neuroscience Letters, 413, 274-278.

[29]   Singh, M., Khan, A.J., Shah, P.P., Shukla, R., Khanna, V.K. and Parmar, D. (2008) Polymorphism in environment responsive genes and association with Parkinson disease. Molecular and Cellular Biochemistry, 312, 131-138.

[30]   Kiyohara, C., Miyake, Y., Koyanagi, M., Fujimoto, T., Shirasawa, S., Tanaka, K., et al. (2010) GST polymorphisms, interaction with smoking and pesticide use, and risk for Parkinson’s disease in a Japanese population. Parkinsonism & Related Disorders, 16, 447-452.

[31]   Biswas, A., Sadhukhan, T., Bose, K., Ghosh, P., Giri, A.K., Das, S.K., et al. (2012) Role of glutathione Stransferase T1, M1 and P1 polymorphisms in Indian Parkinson’s disease patients. Parkinsonism & Related Disorders, 18, 664-665.

[32]   Goldman, S.M., Kamel, F., Ross, G.W., Bhudhikanok, G.S., Hoppin, J.A., Korell, M., et al. (2012) Genetic modification of the association of paraquat and Parkinson’s disease. Movement Disorders, 27, 1652-1658.

[33]   Cornetta, T., Patrono, C., Terrenato, I., De Nigris, F., Bentivoglio, A.R., Testa, A., et al. (2013) Epidemiological, clinical, and molecular study of a cohort of Italian Parkinson disease patients: association with glutathione-S-transferase and DNA repair gene polymorphisms. Cellular and Molecular Neurobiology, 33, 673-680.

[34]   Perez-Pastene, C., Graumann, R., Diaz-Grez, F., Miranda, M., Venegas, P., Godoy, O.T., et al. (2007) Association of GST M1 null polymorphism with Parkinson’s disease in a Chilean population with a strong Amerindian genetic component. Neuroscience Letters, 418, 181-185.

[35]   Nicholl, D.J., Bennett, P., Hiller, L., Bonifati, V., Vanacore, N., Fabbrini, G., et al. (1999) A study of five candidate genes in Parkinson’s disease and related neurodegenerative disorders. European Study Group on Atypical Parkinsonism. Neurology, 53, 1415-1421.

[36]   Harada, S., Fujii, C., Hayashi, A. and Ohkoshi, N. (2001) An association between idiopathic Parkinson’s disease and polymorphisms of phase II detoxification enzymes: Glutathione S-transferase M1 and quinone oxidoreductase 1 and 2. Biochemical and Biophysical Research Communications, 288, 887-892.

[37]   Vilar, R., Coelho, H., Rodrigues, E., Gama, M.J., Rivera, I., Taioli, E. and Lechner, M.C. (2007) Association of A313 G polymorphism (GSTP1*B) in the glutathione-Stransferase P1 gene with sporadic Parkinson’s disease. European Journal of Neurology, 14, 156-161.

[38]   De Palma, G., Dick, F.D., Calzetti, S., Scott, N.W., Prescott, G.J., Osborne, A., Haites, N., Mozzoni, P., Negrotti, A., Scaglioni, A. and Mutti, A. (2010) A case-control study of Parkinson’s disease and tobacco use: Gene-tobacco interactions. Movement Disorders, 25, 912-919.

[39]   Pemble, S., Schroeder, K.R., Spencer, S.R., Meyer, D.J., Hallier, E., Bolt, H.M., Ketterer, B. and Taylor, J.B. (1994) Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochemical Journal, 300, 271-276.

[40]   Seidegard, J. and Pero, R.W. (1988) The genetic variation and the expression of human glutathione transferase mu. Klinische Wochenschrift, 66, 125-126.

[41]   Button, K.S., Ioannidis, J.P., Mokrysz, C., Nosek, B.A., Flint, J., Robinson, E.S. and Munafò, M.R. (2013) Power failure: Why small sample size undermines the reliability of neuroscience. Nature Reviews Neuroscience, 14, 365-376.

[42]   Xu, W.D., Zhou, M., Peng, H., Pan, H.F. and Ye, D.Q. (2013) Lack of association of IL-6 polymorphism with rheumatoid arthritis/type 1 diabetes: A meta-analysis. Joint Bone Spine, 80, 477-481.

[43]   Tao, J.H., Zou, Y.F., Feng, X.L., Li, J., Wang, F., Pan, F.M. and Ye, D.Q. (2011) Meta-analysis of TYK2 gene polymorphisms association with susceptibility to autoimmune and inflammatory diseases. Molecular Biology Reports, 38, 4663-4672.

[44]   Excoffier, L., Laval, G. and Schneider, S. (2005) Arlequin (version 3.0): An integrated software package for population genetics data analysis. Evolutionary Bioinformatics Online, 1, 47-50.

[45]   Coory, M.D. (2010) Comment on: Heterogeneity in metaanalysis should be expected and appropriately quantified. International Journal of Epidemiology, 39, 932.

[46]   Kawalec, P., Mikrut, A., Wisniewska, N. and Pilc, A. (2013) The effectiveness of tofacitinib, a novel Janus kinase inhibitor, in the treatment of rheumatoid arthritis: A systematic review and meta-analysis. Clinical Rheumatology, 32, 1415-1424.

[47]   Jamshidi Ardeshiri, M., Moosazadeh, M., Feizi Masouleh M., Kiani, A. and Fakhri, M. (2013) Prevalence of smoking in 15-64 years old population of north of iran: Meta-analysis of the results of non-communicable diseases risk factors surveillance system. Acta Medica Iranica, 51, 494-500.

[48]   Gibson, E., Fenster, A. and Ward, A.D. (2013) The impact of registration accuracy on imaging validation study design: A novel statistical power calculation. Medical Image Analysis, 17, 805-815.

[49]   Han, J., Won, E.J., Hwang, D.S., Rhee, J.S., Kim, I.C. and Lee, J.S. (2013) Effect of copper exposure on GST activity and on the expression of four GSTs under oxidative stress condition in the monogonont rotifer, Brachionus koreanus. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 158, 91-100.

[50]   Martin, N.J., Collier, A.C., Bowen, L.D., Pritsos, K.L., Goodrich, G.G., Arger, K., Cutterc, G. and Pritsosa, C.A. (2009) Polymorphisms in the NQO1, GSTT and GSTM genes are associated with coronary heart disease and biomarkers of oxidative stress. Mutation Research, 674, 93-100.

[51]   Canbay, E., Dokmetas, S., Canbay, E.I., Sen, M. and Bardakci, F. (2003) Higher glutathione transferase GSTM1 0/0 genotype frequency in young thyroid carcinoma patients. Current Medical Research and Opinion, 19, 102-106.

[52]   Tsabouri, S.E., Georgiou, I., Alamanos, I. and Bourantas, K.L. (2000) Increased prevalence of GSTM(1) null genotype in patients with myelodysplastic syndrome: A casecontrol study. Acta Haematologica, 104, 169-173.

[53]   Park, L.Y., Muscat, J.E., Kaur, T., Schantz, S.P., Stern, J.C., Richie Jr., J.P. and Lazarus, P. (2000) Comparison of GSTM polymorphisms and risk for oral cancer between African-Americans and Caucasians. Pharmacogenetics, 10, 123-131.

[54]   Garte, S., Gaspari, L., Alexandrie, A.K., Ambrosone, C., Autrup, H., Autrup, J.L., et al., (2001) Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiology, Biomarkers & Prevention, 10, 1239-1248.

[55]   Tan, E.K., Khajavi, M., Thornby, J.I., Nagamitsu, S., Jankovic, J. and Ashizawa, T. (2000) Variability and validity of polymorphism association studies in Parkinson’s disease. Neurology, 55, 533-538.