Association Between MAPT Gene And Idiopathic Parkinson’s Disease: A Meta-analysis

Background：Parkinson’s disease (PD) is a common progressive, age related,chronic, degenerative neurologic disorder in central nervous system characterized by atremor that is maximal at rest, postural instability, stooping posture, rigidity, slownessof movements, and a masklike facial expression. Pathologic features of PD include lossof melanin containing neurons in the substantia nigra and other pigmented nuclei of thebrainstem. Intracytoplasmic inclusion bodies can be found in the substantia nigra andlocus coeruleus and the presence of Lewy bodies is the histological marker of thedegenerative changes in Parkinson’s disease. There are more than2million PD patientsin china, with a total PD prevalence rate of2.1%, prevalence rate of male over65is1.7%, and female is1.6%.with PD cannot be cure, it made an enormous impact withhuman`s health and society economy. The etiology and pathogenesis of idiopathic PDare not clear, it influence by both genetic factors and environmental factors, a lot ofgene were related to PD, for example PSP、CBD、FTD、FiD、FTDP-17and MAPT.Microtubule-associated protein tau (MAPT) codes for Tau, Tau is amicrotubule-associated proteins that are mainly expressed in neurons and plays a centralrole in microtubule assembly and maintenance.Within the gene, two distinct two distincthaplotypes H1and H2extend the over entire gene. Recent evidence suggests that MAPT gene H1/H1genotype is significantly associated with risk for PD, but someresearcher produced conflicting results. The association between H1/H2genotype andH1/H2genotype and PD is unclear.Objective：To provide more information on whether the MAPT gene H1/H1,H1/H2, H2/H2genotype is associated with idiopathic Parkinson’s disease.Methods：We searched MEDLINE, The Cochrane Library CENTRAL, sciencecitation index,EMBASE, Medline, CNKI and Wangfang DATA until December2013,using PRISMA search method. We searched for all additional studies in thereferences of any identified publications. Based on strict inclusion and exclusion criteria,two review authors independently assessed study quality and extracted relevantinformation. All inconsistencies were resolved by consensus between authors and wereexplained.We extracted data on first author’s name, year of publication, country of the study,gender, race, PD diagnostic criteria, control selection, the frequencies of MAPT geneH1/H1,H1/H2and H2/H2genotype among cases and controls, if available, ages ofcases at the onset of PD and ages of examination with control. Using endnote tomanagement research, Hardy-Weinberg equilibrium (HWE) was performed byDeFinetti program. Using Newcastle-Ottawa Scale（NOS）to evaluated study quality,only studies over5scores can included in Meta-analysis. The Q test was also used toevaluate the degree of heterogeneity between studies, and I2was used as a measure todescribe the percentage of variability in different studies resulting from totalheterogeneity. The strength of association between MAPT gene H1/H1,H1/H2,H2/H2genotype and idiopathic Parkinson’s disease was assessed by cruds odd ratios and ORscorresponding95%CI, All analyses were performed using Review Manager Version5.1and Stata12.0. We also performed subgroup analyses according to diagnose criteria andresources. Fixed effect summary odds ratios were performed using the Mantel–Haenszelmethod, and the random effect summary odds ratios were performed using theDerSimonian and Lair method, the influence of each studie on the summary OR wasevaluated by reestimating and plotting the summary OR in the absence of each study. In addition, funnel plot and Harbord linear regression method were calculated to evaluatepublication bias.Results：A total of10studies included in Meta-analysis, involving3365PDpatients and2979controls, all studies was case-control design. For geographic source,7from Europe,2from USA and1form Australian, most of cases and controls arecaucasian white. All control individuals were free of Parkinsonism or family history,and conform to the Hardy-Weinberg equilibrium. Q test results (P>0.10) and I2showsno significant heterogeneity. Meta-analysis shows MAPT gene H1/H1genotype issignificantly associated with risk for PD [OR=1.55,95CI（1.39,1.73），P <0.00001],MAPT gene H1/H2genotype is significantly associated with reduce risk for PD[OR=0.69,95CI（0.61,0.78），P <0.00001], MAPT gene H2/H2genotype is significantlyassociated with reduce risk for PD [OR=0.72,95CI（0.55,0.94），p=0.01].Subgroupanalysis according to diagnose criteria and resources shows no significant difference.Similar associations were observed in fixed-effect model and random-effect model,reestimating and plotting the summary odds ratio in the absence of each study alsoshows no significant difference. In addition, funnel plot was symmetrical in general,Harbord linear regression shows for MAPT gene H1/H1genotype t=0.43，P=0.677，95%CI（-1.64,2.39）；for H1/H2genotype t=0.01，P=0.992，95%CI（-1.63,1.65）；for H2/H2genotype t=1.10，P=0.312，95%CI（-1.07,2.84）,no significant publicationbias was observed.Conclusion：1.MAPT gene H1/H1genotype is significantly associated with risk forParkinson’s disease.2.MAPT gene H1/H2and H2/H2genotype is significantlyassociated with reduce risk for Parkinson’s disease, but need further research.