The Study On GAK/DGK-? Genotype And Clinical Phenotype Of Parkinson's Disease

BackgroundSporadic Parkinson's disease(sPD)is a chronic neurodegenerative disease that mainly affects the elderly.With the rapid increase of population aging,the number of sPD in China is increasing gradually.At present,the recognized risk factors of sPD include genetic and environmental factors.Genome-wide association analysis showed that the GAK/DGK-?/IDUA region of chromosome 4p16.3 was one of the three major risk loci for Parkinson's disease(PD),but the specific gene and risk mechanism were not clear.At present,there are no reports about the SNP polymorphisms of GAK/TMEM175/DGK-? gene,including base substitution,transversion,deletion and insertion,which are related to the risk of sPD.Therefore,the SNP loci in GAK/TMEM175/DGK-? region of sporadic Parkinson's disease in China were detected and their clinical phenotypes were analyzed to lay a foundation for the diagnosis of sporadic Parkinson's disease.ObjectivesTo establish a human whole blood gene library and detect the SNP loci of GAK/TMEM175/DGK-? gene in sporadic PD patients,and to explore the association between sporadic PD patients and SNP polymorphism and clinical manifestations,so as to lay a foundation for the diagnosis of Parkinson's disease.MethodsFrom October 2017 to February 2019,patients with motor disorders and Parkinson-like symptoms were collected from Department of Neurology,First Affiliated Hospital of Xinxiang Medical College.Peripheral venous blood was extracted,genome was extracted,and primers corresponding to SNP loci were designed.The target fragments were obtained by PCR amplification and sequenced,and the results were compared and analyzed.At the same time,clinical data of patients were collected,including demographic basic information,motor symptoms scale score and non-motor symptoms scale score.Statistical software was used to analyze and sort out.In addition,the whole blood of healthy people in physical examination department was collected,and the corresponding SNP loci were amplified and sequenced for comparative analysis.ResultsA total of 50 PD patients and 50 healthy controls were included in this study.(1)The analysis of rs11248051 and rs1564282 loci of GAK gene showed that the wild genotype of rs11248051 was G/G.Six mutations were detected in PD patients,four was heterozygous mutation,which was A/G,two was homozygou mutation,the genotype was A/A,and four was A/G in healthy people.There was no statistical difference between the two genotypes(P=0.505).In addition,a homozygou mutant A/A was detected in the wild genotype G/G at rs1564282 locus.There was no significant difference between the two groups(P=1).(2)The analysis of rs6599388,rs142821586,rs6599389 and rs34311866 loci in TMEM175 showed that the wild genotype of rs6599388 was C/C,35 mutation was detected in PD patients,6 was homozygou mutation G/G,29 was heterozygou mutations C/T.27 mutation was found in healthy people,of which 10 was homozygou mutation T/T and 17 were heterozygou mutation C/T.Meaning(P = 0.099).The wild genotype of rs142821586 was C/C,four cases of mutation were detected in PD patients,genotype A/C,two cases of mutation were found in healthy people.There was no significant difference between the two groups(P=0.678).In addition,TC base deletion was detected at the SNP locus,with genotype TC/-,twelve cases were found in PD patients and 13 cases in the control group,with no statistical significance(P=0.817).The wild genotype of rs6599389 was G/G,sixteen mutation was detected in PD patients,10 person were A/G,6 person were A/A,and 7 person were found in healthy people,the genotype was A/G,P=0.032.The wild genotype of rs34311866 locus was T/T.,six cases of mutation were detected in PD patients,three cases were C/C and three cases were C/T,five cases of mutation were found in healthy people,and the genotype was C/T.There was no significant difference between the two groups(P=0.749).(3)The analysis of rs11248060 of DGK-? gene showed that the wild genotype was G/G,and 13 gene mutations was detected in PD patients,including 11 cases were A/G,2 cases were A/A and 4 cases A/G mutations in healthy people.There was a significant difference between the two genotypes(P=0.017).(4)In TMEM175 gene,new gene fragment were found in both patient and healthy person,and 3 cases in patients and healthy persons respectively.(5)rs11248060 was included in the logistic linear regression model,? = 1.384,OR = 1.384,P = 0.026,P < 0.05,95% CI(0.074-0.846),indicating that rs11248060 gene polymorphism may be a high risk factor for PD.(6)The polymorphism of TMEM175 rs6599389 was correlated with tremor symptoms in Parkinson's disease patients,,?=1.601,P=0.015,OR=4.959,95%CI(1.364-18.034),P<0.05,the mutation of rs6599389 may be a high risk factor for tremor.Conclusions1.The polymorphisms of GAK rs11248051 and GAKrs1564282 may not be associated with the sporadic Parkinson's disease in Han population in northern Henan.2.TMEM175 rs65 Henan,and the mutation of rs65999389 is associated with sporadic Parkinson's disease in the Han population of northern9389 may be a high risk factor for tremor.The polymorphisms of SNPs about TMEM175 rs6599388,rs142821586 and rs34311866 may not be associated with sporadic Parkinson's disease in Han population in northern Henan.3.The significance of the new gene fragment "TG AG GC AG CC TG TC AT GG CA GT CC CAT" found in TMEM175 gene remains to be explored.4.DGK-? rs11248060 may be associated with sporadic Parkinson's disease in Han population in northern Henan.