ATP13A2 Gene Polymorphism And Difference LncRNA Expression Profile Of Parkinson’s Disease In Xinjiang And Its Regulation Mechanism

Objectives: 1To investigate the risk factors of Parkinson’s disease(PD)in Xinjiang.2 To investigate the polymorphism of ATP13A2 gene in PD patients in Xinjiang.3 Through the analysis of the results of lnc RNA microarray in Xinjiang PD and healthy control group,the expression profile of lnc RNAs of PD was established;the lnc RNA which regulates ATP13A2 gene was found,and the lnc RNAs with differential expression were screened from lnc RNA microarray.Methods:1Analysis of PD risk factors in Xinjiang: 218 patients with PD;232 healthy controls.All subjects completed the basic condition questionnaire,Hamilton Anxiety(HAMA),Hamilton Depression(HAMD),and Montreal Cognitive Assessment Scale(Mo CA),all of which performed triglyceride(TG),total cholesterol(TC),and high density.Lipoprotein HDL-c),low density lipoprotein(LDL-c),uric acid(UA),homocysteine(Hcy),neutrophils(NEU),eosinophils(EOS),basophils Cell(BAS),lymphocyte(LY),and monocyte(MO)levels were measured using statistical methods including chi-square test and multiple logistic regression analysis to analyze PD risk factors.2.ATP13A2 gene polymorphism analysis of PD patients in Xinjiang: 218 patients with PD and 232 patients with healthy adults.Sanger DNA gene sequencing was used to analyze the polymorphism of ATP13A2 gene rs56367069,rs56379718,rs151117874,rs147277743 and rs2076603.3.Using lnc RNA gene chip technology to detect lnc RNA expression in PD group and healthy control group,lnc RNA gene chip expression profiling,signal pathway analysis and target gene prediction results analysis of PD group lnc RNA chip results,find lnc RNA regulating ATP13A2 gene;expand After the sample size,real-time PCR was used to verify the expression of differential lnc RNAs in the peripheral blood of the PD group and the lnc RNA that regulates the ATP13A2 gene.Results:1.HAPD,HAMA,TC,LDL-c,HCY,and MO in the PD group were significantly higher than those in the control group.There was significant difference between the two groups(P<0.05).The HDL-c,UA,and LY in the PD group were significantly lower than those in the control group,and the difference between the two groups was statistically significant(P<0.05).There were no significant differences in TG,NEU,EO and BA between the PD group and the control group.There was no significant difference between the two groups(P>0.05).In the multivariate analysis,women,tea drinking,TC,HDL-c,LDL-c,UA,HCY,LY,MO,HAMD,HAMA,coffee drinking,and pesticide exposure history were associated with PD(P<0.05).Among the risk factors were: no-tea history OR value and 95%CI: 2.13(1.02-4.45);TC OR value and 95%CI: 2.33(1.45-3.72);LDL-c OR value and 95%CI is: 3.09(1.72-5.58);HCY OR value and 95%CI are:1.21(1.14-1.28);MO OR value and 95%CI: 34.29(3.10-379.04);HAMD OR value and 95 The%CI was:1.05(1.00-1.10);the OR value of the HAMA and 95%CI was:1.14(1.07-1.21);the OR value of the history of no coffee and 95%CI was 3.16(1.48-6.76).The protective factors associated with PD were: female OR value and 95%CI:0.42(0.21-0.84);HDL-c OR value and 95%CI:0.04(0.01-0.12);UA OR value and The 95%CI was0.99(0.99-1.00);the OR value of LY and 95%CI was:0.37(0.22-0.63);the OR value without pesticide contact history and 95%CI was0.28(0.10-0.82).2.Of the 218 patients with PD,only one patient with rs147277743(Ala746Thr)genotype had AG type(Fig.2-2A),and the patient had early-onset Parkinson’s disease(EOPD);the remaining 217 patients with PD had genotypes.GG type,no AA type was found.No mutation was observed in the rs56367069(Arg294Gln)site,the rs56379718(Gly49Ser)site,and the rs151117874(Thr12Met)site of the ATP13A2 gene.There are three types of rs2076603 locus genotypes: AA,AG and GG.Hierarchical analysis: In male dominant models,the risk of PD in GG or AG carriers was0.505 times higher than that of AA carriers(P<0.05).In the male allelic model,the A allele was protected by PD.Factor,the risk of PD with A allele carriers was0.612 times higher than that of carriers carrying G alleles(P<0.05);in the allelic model older than 50 years,the A allele was a protective factor for PD.The risk of PD in carriers carrying the A allele was0.751 times higher than that of the G-bearing allele(P<0.05).3.By analyzing the results of lnc RNA gene chip,PD differential lnc RNA expression profile was established.Compared with the control group,there were 98 differentially expressed lnc RNAs in the PD group,of which 61 lnc RNA expression was up-regulated and 37 lnc RNA expression was down-regulated;PD group and Compared with the healthy control group,there were153 differentially expressed m RNAs,of which118 were up-regulated and 35 were down-regulated.Compared with the healthy control group,the PD groups in Xinjiang were screened for significant differences in the expression of lnc RNA: uc.175+,uc001 vdo.1,XR＿429399.1,RNA94965|RNS＿47＿198,TCONS＿00023421,ENST00000430770.1,ENST00000533322.1,TCONS＿00022787,ENST00000517983.1,ENST00000435434.1,TCONS＿00009962.The m RNAs that expressed significant differences were: EGR1,CX3CR1,PAX5,TNFRSF13 C,BLK,F2 R,TRIM13,LRRK2,ITPKB,ATP13A2.A total of 56 lnc RNAs that regulate the ATP13A2 gene were found.According to the FC value,the P value was statistically significant.The lnc RNA that regulates the ATP13A2 gene was found.lnc RNA RNA94965|RNS＿47＿198 can down-regulate the expression of ATP13A2 gene.The11 lnc RNAs and11 m RNAs between PD patients and healthy controls were verified by q RT-PCR.The results showed that the expression changes of the validation targets in each group were consistent with the experimental results of the transcriptomics microarray detection technique.Conclusion:1.This study found that women,tea history,coffee history,high uric acid levels,LY in inflammatory cells are protective factors for PD;pesticide exposure history,high Hcy levels,anxiety,depression,MO in inflammatory cells High TC and high LDL-c are harmful factors in the pathogenesis of PD.2.The mutation rate of 2ATP13A2 gene rs147277743(Ala746Thr)was1/218,and the mutation frequency was0.46%.Our study found that rs56367069(Arg294Gln)locus and rs56379718(Gly49Ser)were not found in 218 PD cases and 234 control groups.The locus,rs151117874(Thr12Met)locus polymorphism is consistent with the results of the current study on the low frequency of ATP13A2 gene mutation.3.Through the analysis of lnc RNA gene chip,the differential lnc RNA expression profile of PD was established;the population-level verification of differentially expressed lnc RNA was consistent with the microarray detection results,and it can be used as a clinical biomarker for the diagnosis of PD.