Association Between Dopamine Transporter Gene Polymorphism And Distribution Of Dopamine Transporters In The Brain Of Patients With Parkinson’s Disease

Objective:To investigate the correlation between dopamine transporter protein gene（SLC6A3）polymorphisms and dopamine transporter uptake values in Parkinson’s patients,and to explore the role of SLC6A3 gene rs40184 and rs393795 locus polymorphisms in the development of PD to facilitate early intervention and the selection of more targeted treatment options for Parkinson’s patients.Methods:1.Genotyping:27 outpatients or inpatients with PD diagnosed by the Department of Neurology of our hospital and 25 normal controls were collected,all subjects signed an informed consent form,peripheral venous blood was collected,DNA was extracted,and polymerase chain reaction（PCR）-ligation detecyion reaction（LDR）to genotype the rs40184 and rs393795 loci of SLC6A3 gene,calculate the genotype frequencies of rs40184 and rs393795 loci in subjects,and analyze whether rs40184 and rs393795 loci are PD risk loci.2.¹¹C-CFT PET/CT data acquisition:PD patients included in the experiment were staged by Hoehn-Yahr（H-Y）grading criteria for disease severity,（≤2.0 grade for early PD group,>2.0 grade for advanced PD group）,¹¹C-CFT PET/CT brain imaging was performed,the ROI technique was used to outline bilateral caudate nucleus,anterior shell nucleus,posterior shell nucleus and cerebellum,and the uptake values of each region were calculated according to the formula We compared the differences of DAT uptake values in different parts of the neostriatal region between early PD and late PD groups,and investigated the correlation between SLC6A3 gene polymorphisms and DAT uptake values in combination with each locus genotyping,and further analyzed the effects of SLC6A3 gene rs40184 and rs393795locus polymorphisms on the distribution of DAT in the brain and disease development of PD patients.The impact of SLC6A3 gene polymorphisms on DAT distribution and disease development in the brain of PD patients was investigated.Results:I.Genotype frequency distribution in control and PD groupsThe genotype distribution of the SLC6A3 gene at the rs40184 and rs393795 loci were in accordance with the Hardy-Weinberg equilibrium law.rs40184 locus:two alleles,A and G,and three genotypes,AA,AG and GG,with statistically significant differences in genotype frequencies between the control and PD groups（χ²=7.550,P=0.023<0.05）.rs393795 locus:two alleles,A and C,and three genotypes,AA,CA and CC,with statistically significant differences between the control and PD groups（χ²=7.395,P=0.023<0.05）.The rs393795 locus had two alleles,A and C,and three genotypes,AA,CA and CC,with statistically significant differences in genotype frequencies between the control group and the PD group（χ²=7.395,P=0.048<0.05）.II.¹¹C-CFT PET/CT imaging results（1）Comparison of bilateral neostriatal DAT uptake values between early PD group and late PD groupOn ¹¹C-CFT brain imaging,the distribution of radioactivity in the neostriatal region in the early PD group showed decreased uptake and asymmetry,with lesions affecting the contralateral side first,showing a"posterior-to-foreward"pattern of disease progression,with the posterior,anterior,and caudate nuclei in that order.There was a statistically significant difference in DAT uptake values in the early PD group in the anterior shell nucleus compared with the contralateral side（P<0.001）.In the late PD group,DAT uptake values were significantly lower in the anterior shell nucleus,posterior shell nucleus and caudate nucleus bilaterally,and the difference in uptake values was not statistically significant when compared bilaterally（P>0.05）.Compared with patients with early PD,the brain DAT uptake values were significantly reduced in patients with late PD,with statistically significant differences（P<0.05）,except for the contralateral anterior shell nucleus,the posterior shell nucleus on the side of initiation,and the contralateral posterior shell nucleus.（2）Comparison of DAT uptake values of rs40184 gene polymorphism in bilateral neostriatal regions between early PD group and late PD groupThe GG subgroup in the late PD group had significantly lower DAT uptake values in the caudate nucleus on the onset side and the anterior shell nucleus on the onset side compared with the GG subgroup in the early PD group,and the differences were statistically significant（P=0.025;P=0.033<0.05）,and the posterior shell nucleus on the onset side,the contralateral caudate nucleus,the contralateral anterior shell nucleus and the contralateral posterior shell nucleus all had a tendency to decrease,but the differences were not statistically significant（P>0.05）.In the late PD group,bilateral DAT uptake values were significantly lower in the GG subgroup compared with the AA/AG subgroup in the anterior shell nucleus on the onset side,the posterior shell nucleus on the onset side,the contralateral anterior shell nucleus and the contralateral posterior shell nucleus（P=0.008;P=0.008<0.05;P=0.014<0.05;P=0.019<0.05）;DAT uptake values in the caudate nucleus on the onset side and the contralateral caudate nucleus also had The differences between the two subgroups in the early PD group were not significant（P>0.05）.（3）Comparison of DAT uptake values of rs393795 gene polymorphism in bilateral neostriatum between early PD group and late PD groupBilateral DAT uptake values were reduced in both the AA-type subgroup and the CA/CC-type subgroup in the late PD group compared with the early PD group,but lacked statistical significance（P>0.05）.In the late PD group,DAT uptake values in the contralateral posterior shell nucleus were reduced in the AA subgroup compared with the CA/CC subgroup（P=0.040<0.05）;DAT uptake values in the rest of the neostriatum also tended to be reduced,but the difference was not statistically significant（P>0.05）;the difference in bilateral DAT uptake values between the two subgroups in the early PD group was not significant（P>0.05）.Conclusions:The rs40184 and rs393795 polymorphic loci of the SLC6A3 gene are risk loci for PD.rs40184 and rs393795 polymorphic loci of the SLC6A3 gene correlate with the distribution of DAT and may affect the development of PD by influencing bilateral neostriatal DAT uptake.rs40184 locus GG carriers and rs393795 locus AA carriers have a further decrease in DAT uptake values as PD DAT uptake values were further reduced as the patients progressed.