Association between Q115L of PINK1 Gene Polymorphism and Parkinson’s Disease: A Meta-Analysis

Author(s): Zhicheng Liu, Zhiguo Liu

Many case–control studies have researched the associations between PINK1 Q115L polymorphisms and the risk of Parkinson’s disease (PD), but the results exist controversies. We performed a meta-analysis to assess the possible association between the PINK1 Q115L gene polymorphisms and PD. Here we searched the Pubmed, CNKI, CBM and Web of Science databases up to 2015 to identify published related studies. The meta-analysis was then conducted to analysis the possible associations between the PINK1 Q115L polymorphisms and PD. A total of six studies were included in the meta-analysis. The crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated to evaluate the association. Heterogeneity among studies was evaluated using the I2 and Egger's test was used to evaluate publication bias. Sensitivity analysis was also performed. After exclusion of articles deviating from HWE in controls. The meta-analysis also showed no significant association between the T allele and increased risk of PD in allele model (FEM: OR=0.790, 95% CI=0.568-1.098); dominant model (FEM: OR=1.344, 95% CI=0.952-1.897); heterozygote model (FEM: OR=0.736, 95% CI=0.519-1.043). In subgroup analysis, for Caucasian, there was no significantly association in all three models. Our suggested that the PINK1 Q115L polymorphism might not be associated with PD.

PINK1, Q115L, Parkinson’s Disease, Meta-Analysis, Mitochondria

1. Van Den Eeden, S.K., et al., Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. Am J Epidemiol, 2003. 157(11): p. 1015-22.
2. Olanow, C.W., M.B. Stern, and K. Sethi, The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology, 2009. 72(21 Suppl 4): p. S1-136.
3. Tolleson, C.M. and J.Y. Fang, Advances in the mechanisms of Parkinson's disease. Discov Med. 15(80): p. 61-6.
4. Varcin, M., et al., Oxidative stress in genetic mouse models of Parkinson's disease. Oxid Med Cell Longev. 2012: p. 624925.
5. Blesa, J., et al., Classic and new animal models of Parkinson's disease. J Biomed Biotechnol. 2012: p. 845618.
6. Gwinn-Hardy, K., Genetics of parkinsonism. Mov Disord, 2002. 17(4): p. 645-56.
7. Pankratz, N. and T. Foroud, Genetics of Parkinson disease. Genet Med, 2007. 9(12): p. 801-11.
8. Valente, E.M., et al., Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science, 2004. 304(5674): p. 1158-60.
9. Sim, C.H., et al., C-terminal truncation and Parkinson's disease-associated mutations down-regulate the protein serine/threonine kinase activity of PTEN-induced kinase-1. Hum Mol Genet, 2006. 15(21): p. 3251-62.
10. Valente, E.M., et al., PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann Neurol, 2004. 56(3): p. 336-41.
11. Bonifati, V., et al., Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes. Neurology, 2005. 65(1): p. 87-95.
12. Healy, D.G., et al., PINK1 (PARK6) associated Parkinson disease in Ireland. Neurology, 2004. 63(8): p. 1486-8.
13. Brooks, J., et al., Parkin and PINK1 mutations in early-onset Parkinson's disease: comprehensive screening in publicly available cases and control. J Med Genet, 2009. 46(6): p. 375-81.
14. Ishihara-Paul, L., et al., PINK1 mutations and parkinsonism. Neurology, 2008. 71(12): p. 896-902.
15. Klein, C., et al., PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset parkinsonism. Eur J Hum Genet, 2005. 13(9): p. 1086-93.
16. Schlitter, A.M., et al., Exclusion of PINK1 as candidate gene for the late-onset form of Parkinson's disease in two European populations. J Negat Results Biomed, 2005. 4: p. 10.
17. Toft, M., et al., PINK1 mutation heterozygosity and the risk of Parkinson's disease. J Neurol Neurosurg Psychiatry, 2007. 78(1): p. 82-4.
18. Higgins, J.P., et al., Measuring inconsistency in meta-analyses. BMJ, 2003. 327(7414): p. 557-60.
19. Peters, J.L., et al., Comparison of two methods to detect publication bias in meta-analysis. JAMA, 2006. 295(6): p. 676-80.
20. Huxley, N., et al., A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer. Health Technol Assess, 2015. 19(2): p. v-xxv, 1-215.
21. Patsopoulos, N.A., E. Evangelou, and J.P. Ioannidis, Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol, 2008. 37(5): p. 1148-57.
22. Petit, A., et al., Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations. J Biol Chem, 2005. 280(40): p. 34025-32.
23. Duchen, M.R., A. Surin, and J. Jacobson, Imaging mitochondrial function in intact cells. Methods Enzymol, 2003. 361: p. 353-89.
24. Onyango, I.G., Mitochondrial dysfunction and oxidative stress in Parkinson's disease. Neurochem Res, 2008. 33(3): p. 589-97.