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The Association Analysis of DRD2and DAT Genetic Polymorphisms with the Susceptibility of PD and Their Effects on PD Treatment

Author: NingWei
Tutor: LiuJie
School: Central South University
Course: Pharmacology
Keywords: dopamine transporter dopamine D2receptor genepolymorphism Madopa pramipexole Parkinson’s disease
CLC: R742.5
Type: Master's thesis
Year: 2013
Downloads: 7
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Abstract


Objectives:The dopamine D2receptor (DRD2) and dopamine transporter (DAT) are key molecules in dopamine pathway.DRD2acts as an important target for anti-Parkinson’s disease drugs. The aims of this study were to explore the distributive characteristics of DRD2rs6275, rs6277, DAT rs3756450T/C and rs6348C/T mutations in Chinese Parkinson’s disease patients and health control subjects, and investigate whether DRD2rs6275C/T, DAT rs27072C/T and rs3756450T/C polymorphisms affect the therapeutic response to Madopa combined with pramipexole in PD patientsMethods:The genotypes of DRD2, DAT ware determined by direct sequencing assay in196Parkinson’s disease patients and144healthy volunteers. Fifty-one patients were grouped by genetypes. They were administered orally Madopa62.5mg bid and pramipexole0.125mg tid for one month, Unified Parkinson Disease Rating Scale (UPDRS) assessments were conducted at baseline and one month after treatment. Improvement by20%or more in the total score on the UPDRS was considered responsive. Statistical analyses were performed by T-test, one-way ANOVA, Wilcoxon rank sum test, and Pearson’sχ2.Results:The genetic polymorphisms of DRD2and DAT genes were consistent with Hardy-Weinberg equilibrium. The frequencies of DRD2rs6275genotypes in Parkinson patients and healthy controls is C/C(20.9%vs16.7%),C/T(57.7%vs54.2%),T/T(21.4%vs29.1%),and allelic frequency is C(49.7%vs43.7%),T(50.3%vs56.3%);The frequencies of DRD2rs6277genotypes in Parkinson patients and healthy controls is C/C(88.8%vs90.3%),C/T(11.2%vs9.7%),and allelic frequency is C(94.4%vs95.1%),T(5.6%vs4.9%);The frequencies of DAT rs3756450genotypes in Parkinson patients and healthy controls is T/T(26.5%vs33.3%),T/C(53.1%vs43.1%),C/C(20.4%vs23.6%),and allelic frequency is T(53.1%vs54.9%)5C(46.9%vs45.1%),There is no significant differences of genotypes frequencies for DRD2rs6275,rs6277and DATrs3756450between the patients and the healthy controls (P>0.05);The variant allelic of rs6348C>T was not detected in Chinese population. One month after treatment in51Parkinson’s disease patients.When the subjects were grouped by DRD2rs6275polymorphism,the response rates for Madopa and pramipexole treatments was significantly higher in T/T group(68.8%) compared with the group containing C allele(P=0.028); When the subjects were grouped by DATrs27072or rs3756450polymorphism, there were no significant differences among three genotypes.Conclusions:DRD2rs6275, rs6277and DATrs3756450polymorphisms were not associated with the susceptibility of PD. The variant allelic of rs6348C>T was not detected in our sample. DRD2rs6275polymorphism was significantly associated with therapeutic efficacy of Madopa combined with pramipexole in Chinese patients with PD. Whereas, DATrs27072and rs3756450polymorphisms were not significantly associated with the therapeutic response to Madopa combined with pramipexole in PD patients.

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Brain diseases > Paralysis agitans syndrome
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