Correlation Study Between PGC-1? Rs2946385 Gene Polym- Orphism With Different Subtypes Of Parkinson's Disease And Non-motor Symptoms

BackgroundIn a Genome-wide meta-analysis of gene expression in brain tissues of PD patients,multiple PGC-1? target genes were found to be downregulated,suggesting that dysfunctional PGC-1? gene plays an important role in the clinical pathogenesis of PD.The activation of PGC-1? gene can increase the expression of subunit encoded by mitochondrial respiratory chain nucleus,which in turn blocks the loss of dopaminergic neurons in mutant ?-synuclein or pesticide rotenone-induced PD cell models.PGC-1?gene is closely associated with mitochondrial dysfunction and oxidative stress,which is an important pathogenesis of PD.There are no reports that PGC-1? gene polymorphism is associated with the risk of PD in populations in northern Henan.ObjectivesTo investigate the association of PGC-1? rs2946385 gene polymorphism with risk of Parkinson's disease,motor symptoms,non-motor symptoms anxiety and cognitive function.Methods86 sporadic PD patients and 86 health examiners in our hospital at the same time were selected,collected clinical data and evaluated the MMSE,HAMA,HAMD,MOCA and UPDRS-III scores.DNA was extracted from peripheral blood.The target gene fragment was amplified by PCR technique and DNA sequenced.The sequences obtained were compared using DNAMAN 6.0 software.Then the mutation rate was counted.The locus was genotyped using Chromas software v2.6.5.Compared the distribution differences of alleles and genotypes between PD group and healthy control one.The PD patients were further divided into AR-PD and TD-PD groups according the UPDRS-III scores.Then analysed the clinical manifestations of different subtypes and the distribution of alleles andgenotypes of the locus.All the data were analyzed by SPSS 25.0 version statistical software.Results(1)There were no significant differences in age,sex between PD group and thecontrol group(P>0.05),but significant differences in cognitive function,anxiety and depression(P<0.05);(2)There were no significant differences in sex,age,course of disease,anxiety,depression,constipation,UPDRS-III scores between the AR-PD group and the TD-PD group(P>0.05),while there was a significant difference in cognitive function(P<0.05);(3)There are three genotypes of PGC-1? gene rs2946385 locus: AA,CA and CC.The distribution of this genotype in the control group,PD group,AR-PD group and TD-PD group was tested in accordance with the Hardy-Weinberg equilibrium(P>0.05);(4)Compared with the control group,there were no significant differences in the locus C allele and CC genotype frequency in the PD group(P>0.05);(5)Compared with the AR-PD group,there were no significant differences in the locus C allele and CC genotype frequency in the TD-PD group(P>0.05);(6)The locus C allele and genotype CC had no significant association with the risk of cognitive decline in patients of PD group,TD-PD group and AR-PD group(P>0.05);(7)The locus C allele and genotype CC had no significant association with the risk of anxietyin patients of PD group,TD-PD group(P>0.05);Significant correlations were observed in anxiety patients of AR-PD group(P<0.05),but after balancing age,sex,course of disease,and UPDRS-III score,the locus was not an independent risk factor for anxiety in patients of AR-PD group(P>0.05);(8)Results of multivariate Logistic regression analysis showed that the severity of motor symptoms in PD patients was an independent risk factor for AR-PD patients with anxiety(P<0.05).The higher the UPDRS-III score,the higher the risk of anxiety in AR-PD patients.Conclusions1.PGC-1? rs2946385 gene polymorphism was not associated with the occurrence of PD,subtypes and the risk of anxiety and cognitive decline.2.AR-PD patients have more risk of cognitive decline than TD-PD patients.3.The severity of motor symptoms in PD patients is an independent risk factor for anxiety in AR-PD patients.