Meta-analysis of tau genetic polymorphism and sporadic progressive supranuclear palsy susceptibility

OBJECTIVE: To quantitatively evaluate the association between tau genetic polymorphism (H-1 and H-2) and susceptibility to sporadic progressive supranuclear palsy (PSP). DATA SOURCES: Relevant Medical Subject Heading terms and text words were used to identify articles from MEDLINE (1966/2010-07), EMBASE (1984/2010-07), and Chinese National Knowledge Infrastructure (1979/2010), as well as references of the retrieved articles. STUDY SELECTION: The selected articles met the following criteria: sporadic PSP case group and healthy control group, as well as genotype frequency (H-1/H-1 and H-1/H-2 + H-2/H-2) in cases and controls. Genotype distribution in the control groups was tested using the Hardy-Weinberg Equilibrium (HWE). Articles irrelevant to HWE were excluded, and a forest plot was performed to combine all selected articles with Review Manager (Version 5.0). MAIN OUTCOME MEASURES: The summary odds ratios and corresponding 95% confidence intervals (95%CI) for tau polymorphism (H-1/H-1 and H-1/H-2 + H-2/H-2) between sporadic PSP case and healthy control groups were estimated using the fixed effects model to assess whether tau genetic polymorphism is associated with sporadic PSP susceptibility. RESULTS: According to inclusion and exclusion criteria, a total of 16 articles, which included 1 337 sporadic PSP cases and 2 073 controls, were used in the study. Two articles were excluded because of deviation from HWE in the control groups. The combined result, based on all studies, showed a significant difference in genotype distribution between cases and controls: H1H1 vs. H1H2 + H2H2 (odds ratio (OR) = 4.98, 95%CI: 3.97-6.23, P < 0.01). Stratifying for geographic distribution of PSP, sporadic PSP cases exhibited a significantly higher frequency of H1H1 genotypes than controls in the United States (OR = 4.07, 95%CI: 3.16-5.25, P < 0.01) and Europe (OR = 8.60, 95%CI: 5.05-14.64, P < 0.01). CONCLUSION: Tau genetic polymorphism is associated with sporadic PSP susceptibility, and geographic distribution might play a role in tau genetic polymorphism and sporadic PSP susceptibility.