Skip to main content
Log in

Null genotype of GSTT1 contributes to increased Parkinson’s disease risk in Caucasians: evidence from a meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Conflicting results in previous case–control studies on the association between Glutathione S-transferase T1 (GSTT1) gene polymorphism and Parkinson’s disease (PD) risk have been reported, so we conducted this meta-analysis. We searched and extracted data from 3 Chinese and 3 English web-based electronic databases to evaluate the associations by odds ratio (OR) and its 95 % confidence interval (CI) under the recessive genetic comparison model (null genotype vs. present genotype). We also conducted subgroup analyses by ethnicity and adjusted status of OR, respectively. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also reanalyzed. When 18 eligible studies (3,963 PD cases and 5,472 controls) were pooled to analyze the association, we found no statistically significant result (OR 1.24, 95 % CI 0.96–1.60). In the subgroup analyses by ethnicity, there was statistically significant association between the null genotype of GSTT1 and PD risk among Caucasians, while the associations were not found among Asians and Latinos. In the subgroup analyses by adjusted status of OR, there were no significant associations both in studies with crude OR and adjusted OR. Meta-analyses and subgroup analyses of larger studies (sample size ≥300) were also confirmed the associations mentioned above. Power analysis indicated only meta-analysis of Caucasians had enough evidence to claim the association. In conclusion, the meta-analysis suggests that the null genotype of GSTT1 contributes to PD risk in Caucasians, and no association in Asians is needed more studies to confirm.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Moore DJ, West AB, Dawson VL, Dawson TM (2005) Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci 28:57–87

    Article  PubMed  CAS  Google Scholar 

  3. Abu-Amero KK, Milcarek B, Bosley TM (2009) GSTM1 and GSTT1 deletion genotypes in various spontaneous optic neuropathies in Arabs. Br J Ophthalmol 93:1101–1104

    Article  PubMed  CAS  Google Scholar 

  4. Zhong S, Yang JH, Liu K, Jiao BH, Chang Z (2012) Null genotype of glutathione S-transferase Tl contributes to colorectal cancer risk in the Asian population: a meta-analysis. J Gastroenterol Hepatol 27:231–237

    Article  PubMed  CAS  Google Scholar 

  5. Hayes JD, Strange RC (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61:154–166

    Article  PubMed  CAS  Google Scholar 

  6. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129

    Article  Google Scholar 

  7. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  PubMed Central  Google Scholar 

  8. Galbraith RF (1988) A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med 7:889–894

    Article  PubMed  CAS  Google Scholar 

  9. Bandmann O, Vaughan J, Holmans P, Marsden CD, Wood NW (1997) Association of slow acetylator genotype for N-acetyltransferase 2 with familial Parkinson’s disease. Lancet 350:1136–1139

    Article  PubMed  CAS  Google Scholar 

  10. De Palma G, Mozzoni P, Mutti A, Calzetti S, Negrotti A (1998) Case–control study of interactions between genetic and environmental factors in Parkinson’s disease. Lancet 352:1986–1987

    Article  PubMed  Google Scholar 

  11. Menegon A, Board PG, Blackburn AC, Mellick GD, Le Couteur DG (1998) Parkinson’s disease, pesticides, and glutathione transferase polymorphisms. Lancet 352:1344–1346

    Article  PubMed  CAS  Google Scholar 

  12. Stroombergen MC, Waring RH (1999) Determination of glutathione S-transferase mu and theta polymorphisms in neurological disease. Hum Exp Toxicol 18:141–145

    Article  PubMed  CAS  Google Scholar 

  13. Rahbar A, Kempkes M, Muller T, Reich S, Welter FL, Meves S, Przuntek H, Bolt HM, Kuhn W (2000) Glutathione S-transferase polymorphism in Parkinson’s disease. J Neural Transm 107:331–334

    Article  PubMed  CAS  Google Scholar 

  14. Ahmadi A, Fredrikson M, Jerregard H, Akerback A, Fall PA, Rannug A, Axelson O, Soderkvist P (2000) GSTM1 and mEPHX polymorphisms in Parkinson’s disease and age of onset. Biochem Biophys Res Commun 269:676–680

    Article  PubMed  CAS  Google Scholar 

  15. Kelada SN, Stapleton PL, Farin FM, Bammler TK, Eaton DL, Smith-Weller T, Franklin GM, Swanson PD, Longstreth WT Jr, Checkoway H (2003) Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson’s disease. Neurosci Lett 337:5–8

    Article  PubMed  CAS  Google Scholar 

  16. Deng Y, Newman B, Dunne MP, Silburn PA, Mellick GD (2004) Case-only study of interactions between genetic polymorphisms of GSTM1, P1, T1 and Z1 and smoking in Parkinson’s disease. Neurosci Lett 366:326–331

    Article  PubMed  CAS  Google Scholar 

  17. Fong C, Cheng C, Wu R (2006) Modification of pesticide exposure in correlation with Glutathione Transferase (GST) polymorphisms for the susceptibility risk of sporadic Parkinson’s diseases. Mov Disord 21:S501–S502

    Google Scholar 

  18. Dick FD, De Palma G, Ahmadi A, Osborne A, Scott NW, Prescott GJ, Bennett J, Semple S, Dick S, Mozzoni P, Haites N, Wettinger SB, Mutti A, Otelea M, Seaton A, Soderkvist P, Felice A (2007) Gene-environment interactions in parkinsonism and Parkinson’s disease: the Geoparkinson study. Occup Environ Med 64:673–680

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Wahner AD, Glatt CE, Bronstein JM, Ritz B (2007) Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson’s disease. Neurosci Lett 413:274–278

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Singh M, Khan AJ, Shah PP, Shukla R, Khanna VK, Parmar D (2008) Polymorphism in environment responsive genes and association with Parkinson disease. Mol Cell Biochem 312:131–138

    Article  PubMed  CAS  Google Scholar 

  21. Kiyohara C, Miyake Y, Koyanagi M, Fujimoto T, Shirasawa S, Tanaka K, Fukushima W, Sasaki S, Tsuboi Y, Yamada T, Oeda T, Miki T, Kawamura N, Sakae N, Fukuyama H, Hirota Y, Nagai M (2010) GST polymorphisms, interaction with smoking and pesticide use, and risk for Parkinson’s disease in a Japanese population. Parkinsonism Relat Disord 16:447–452

    Article  PubMed  CAS  Google Scholar 

  22. Matmurodov RJ, Khalimova KM, Raimova MM (2011) Polymorphism of the genes GSTM1, GSTT1, and environmental factors in the development of Parkinson’s disease among representatives of the Uzbek nationality. Eur J Neurol 18:S501

    Google Scholar 

  23. Goldman SM, Kamel F, Ross GW, Bhudhikanok GS, Hoppin JA, Korell M, Marras C, Meng C, Umbach DM, Kasten M, Chade AR, Comyns K, Richards MB, Sandler DP, Blair A, Langston JW, Tanner CM (2012) Genetic modification of the association of paraquat and Parkinson’s disease. Mov Disord 27:1652–1658

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Biswas A, Sadhukhan T, Bose K, Ghosh P, Giri AK, Das SK, Ray K, Ray J (2012) Role of glutathione S-transferase T1, M1 and P1 polymorphisms in Indian Parkinson’s disease patients. Parkinsonism Relat Disord 18:664–665

    Article  PubMed  Google Scholar 

  25. Cornetta T, Patrono C, Terrenato I, De Nigris F, Bentivoglio AR, Testa A, Palma V, Poggioli T, Padua L, Cozzi R (2013) Epidemiological, clinical, and molecular study of a cohort of Italian Parkinson disease patients: association with glutathione-S-transferase and DNA repair gene polymorphisms. Cell Mol Neurobiol 33:673–680

    Article  PubMed  CAS  Google Scholar 

  26. Pinhel MA, Sado CL, Longo Gdos S, Gregorio ML, Amorim GS, Florim GM, Mazeti CM, Martins DP, Oliveira Fde N, Nakazone MA, Tognola WA, Souza DR (2013) Nullity of GSTT1/GSTM1 related to pesticides is associated with Parkinson’s disease. Arq Neuropsiquiatr 71:527–532

    Article  PubMed  Google Scholar 

  27. Ioannidis JP, Patsopoulos NA, Evangelou E (2007) Uncertainty in heterogeneity estimates in meta-analyses. BMJ 335:914–916

    Article  PubMed  PubMed Central  Google Scholar 

  28. Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, Nelson LM (2003) Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity. Am J Epidemiol 157:1015–1022

    Article  Google Scholar 

  29. Dyba T, Kampenes VB, Sjoberg DIK (2006) A systematic review of statistical power in software engineering experiments. Inf Softw Technol 48:745–755

    Article  Google Scholar 

  30. Chang WW, Su H, He L, Zhao KF, Wu JL, Xu ZW (2010) Association between transforming growth factor-beta1 T869C polymorphism and rheumatoid arthritis: a meta-analysis. Rheumatology (Oxford) 49:652–656

    Article  CAS  Google Scholar 

  31. Ciccone S, Maiani E, Bellusci G, Diederich M, Gonfloni S (2013) Parkinson’s disease: a complex interplay of mitochondrial DNA alterations and oxidative stress. Int J Mol Sci 14:2388–2409

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Zhang Y, Wang ZZ, Sun HM (2012) Lack of association between p.Ser167Asn variant of Parkin and Parkinson’s disease: a meta-analysis of 15 studies involving 2,280 cases and 2,459 controls. Am J Med Genet B 159B:38–47

    Article  Google Scholar 

  33. Wang B, Huang G, Wang D, Li A, Xu Z, Dong R, Zhang D, Zhou W (2010) Null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis. J Hepatol 53:508–518

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dian-Wu Liu.

Additional information

Dan Wang and Jun-Xia Zhai have contributed equally to this work, and should be looked as co-first authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 118 kb)

Supplementary material 2 (DOC 368 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, D., Zhai, JX., Zhang, LM. et al. Null genotype of GSTT1 contributes to increased Parkinson’s disease risk in Caucasians: evidence from a meta-analysis. Mol Biol Rep 41, 7423–7430 (2014). https://doi.org/10.1007/s11033-014-3631-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3631-6

Keywords

Navigation