GRIN2B、SLC6A3、SLC18A2Gene Polymorphisms Associated With The Development Of Dyskinesia In Parkinson’s Disease

Abstract:Background:The dopamine precursor levodopa has been demonstrated to be an effective antiparkinsonian medication for Parkinson’s disease (PD), but long-term therapy with levodopa is complicated by subsequent development of motor complications, such as levodopa-induced dyskinesia (LID).The dyskinesia in PD limited the long-term usability of levodopa and affected the quality of patients’life. The risk factors associated with the development of dyskinesias are gender, age at onset of disease, duration of disease, dose and duration of levodopa treatment. Until now there is few study focus on the factors associated with the development of dyskinesia in PD.Objective:This part of study aims at exploring the relationship between the factors and dyskinesia in PD. Methods:The patients’score on the motor component and ability of daily living (Part II and III) of the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn-Yahr stage were recorded. LID was considered to be present if the patient had a score of1or more on item32of the UPDRS Part IV. Clinical data, including age,gender, age at disease onset, initial clinical manifestation, time when levodopa therapy was started, and current treatment were analyzed between the two groups.Results:Of the412cases,316patients present with PD for at least3years,99of them developed LID by the end of the study. There were statistically significant differences in age at onset of disease, duration of disease, and dose of levodopa treatment, score on UPDRS partⅢ between the two groups.Multivariate logistic regression analysis showed that age at onset of PD, duration of disease, and dose of levodopa were independent risk factors. Conclusion:The results showed that the development of LID was more likely in patients with early onset of disease, a longer duration of PD and a higher daily dose of levodopa. Abstract:Background:Experimental models of dyskinesia in Parkinson’s disease (PD) show that dyskinesia involves abnormal changes on glutamate receptor ionotropic NMDA receptors NR2B subunits. Genetics factors,such as single nucleotide polymorphisms (SNPs) of NMDA receptors NR2B subunits gene, GRIN2B, could contribute to the individual variations in the development of levodopa-induced dyskinesia (LID).Until now there is few study about the GRIN2B gene single nucleotide polymorphisms and the risk of LID in China.Objective:This part of study aims at exploring the relationship between GRIN2B genetic variations and dyskinesia in PD. Methods:In this study, direct DNA sequencing methods and time of flight mass spectrometer were used to detect the316PD patients including99LID and200healthy people of this Han study group,6SNPs of GRIN2B gene were analyzed: rs34315573, rs7301328, rs1805522, rs1806201, rs1806191and rs1805246. Results:The results of the association study of6SNPs in Chinese PD patients and unrelated controls are as follows:1. The rs1806191genotype and allele frequency were less than5%.2.Genotype and allele frequencies of the other5SNPs in PD patients revealed no statistically significant differences from controls.Also, there were no statistically significant differences for the5SNPs between PD LID patients and non-LID patients. Conclusion:In the study group,SNPs (rs34315573, rs7301328, rs1805522, rs1806201and rs1805246) were not related with PD or LID. Abstract:Background:Dopamine transporter (DAT) plays a critical role in transport of dopamine, which are closely related to the mechanism of Parkinson’s disease (PD). The genetic variations of DAT could change transporting of dopamine through influencing the protein expression. Genetics factors, such as DAT gene, SLC6A3would contribute to the individual variations in the development of levodopa-induced dyskinesia (LID). Until now there is few study about the SLC6A3gene single nucleotide polymorphisms and the risk of LID in China.Objective:This part of study aims at exploring the relationship between SLC6A3genetic variations and dyskinesia in PD. Methods:In this study,direct DNA sequencing methods and time of flight mass spectrometer were used to detect the316PD patients including99LID and200healthy people of this Han study group,2SNPs of SLC6A3gene were analyzed: rs6347and rs2270912. Results:The results of the association study of2SNPs in Chinese PD patients and unrelated controls are as follows:1. The frequency for rs2270912in this study group was less than5%.2. Genotype and allele frequencies of the rs6347in PD patients revealed no statistically significant differences from controls. Also, there was no statistically significant difference for the rs6347between PD LID patients and non-LID patients. Conclusion:In the study group, rs6347 was not related with the development of PD or LID. Abstract:Background:Vesicular monoamine transporter subtype2(VMAT2)is important for storing and releasing of dopamine, which also participates in the mechanism of Parkinson’s disease (PD). The genetic variations of VMAT2could change storing and releasing of dopamine and affect the protein expression. Genetics factors, such as VMAT2gene, SLC18A2would contribute to the individual variations in the development of levodopa-induced dyskinesia (LID).Until now there is few study about the SLC18A2gene single nucleotide polymorphisms and the risk of LID in China.Objective:This part of study aims at exploring the relationship between SLC18A2genetic variations and dyskinesia in PD.Methods:In this study, direct DNA sequencing methods and time of flight mass spectrometer were used to detect the316PD patients including99LID and200healthy people of this Han study group,9SNPs SLC18A2gene were analyzed:rs60912143, rs2619095, rs12412905,rs60543597,rs363387,rs363411, rs363420,rs363272and c.116T>C.Results:The results of the association study of9SNPs in Chinese PD patients and unrelated controls are as follows:1.The frequency of c.116T>C was less than5%.2.Genotype and allele frequencies of the6SNPs rs60912143, rs12412905,rs363387, rs363411,rs363420and rs363272) in PD patients revealed no statistically significant differences from controls. Also, there were no statistically significant differences for the6SNPs between PD LID patients and non-LID patients.3.Genotype and allele frequencies of rs2619095and rs60543597in PD patients revealed no statistically significant differences from controls.4.Genotype frequencies of rs2619095and rs60543597showed statistically significant differences between PD LID patients and non-LID patients.Conclusion:1.In the study group, SNPs (rs60912143,rs12412905,rs363387, rs363411,rs363420and rs363272) were not related with PD or LID.2. In the study group, the rs2619095and rs60543597were not related with the development of PD, which were possibly related with the development of LID in PD.