發(fā)布時(shí)間：2018-03-02 12:46

  本文選題：痙攣性斜頸　切入點(diǎn)：多巴胺D5受體　出處：《廣西醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：背景：肌張力障礙的發(fā)生與腦內(nèi)多巴胺、5-羥色胺及乙酰膽堿等神經(jīng)遞質(zhì)的紊亂有關(guān)。痙攣性斜頸的發(fā)病可能與D5受體的基因多態(tài)性相關(guān)。對(duì)痙攣性斜頸患者D5受體基因微衛(wèi)星多態(tài)性研究發(fā)現(xiàn)其等位基因4頻率比對(duì)照組高，提示D5受體的突變可能是痙攣性斜頸的易感因素。D5受體的功能障礙可影響基底節(jié)多巴胺能通路，表明多巴胺受體功能異常與痙攣性斜頸的發(fā)病可能有相關(guān)性。前期研究中為探討多巴胺D5受體基因多態(tài)性與痙攣性斜頸的相關(guān)性，發(fā)現(xiàn)了多巴胺D5受體基因（DRD5基因）的開放閱讀框架ORF上877、1096、1199、1229、1268、1269位點(diǎn)出現(xiàn)單核苷酸位點(diǎn)的突變差異，其均有統(tǒng)計(jì)學(xué)意義，可能與痙攣性斜頸的易感性有關(guān)。 目的：驗(yàn)證痙攣性斜頸前期研究中發(fā)現(xiàn)的DRD5基因中的ORF上877、1096、1199、1229、1268、1269位點(diǎn)的突變是否與其發(fā)病具有相關(guān)性，進(jìn)一步為痙攣性斜頸的診斷提供分子生物學(xué)依據(jù)。 方法：根據(jù)痙攣性斜頸患者前期研究中發(fā)現(xiàn)的ORF上877、1096、1199、1229、1268、1269位點(diǎn)出現(xiàn)單核苷酸位點(diǎn)的突變差異，在6個(gè)位點(diǎn)外圍設(shè)計(jì)內(nèi)、外側(cè)引物，進(jìn)行巢式PCR擴(kuò)增。對(duì)巢式PCR擴(kuò)增后得到目的基因進(jìn)行直接基因測(cè)序，確定每個(gè)樣本出現(xiàn)的基因點(diǎn)突變情況。 結(jié)果：經(jīng)過基因測(cè)序檢測(cè)發(fā)現(xiàn)DRD5基因的ORF上877位點(diǎn)存在單核苷酸突變，由A變異為G，，與前期研究結(jié)果一致。ORF上1096、1199、1229、1268、1269位點(diǎn)無突變。ORF上877位點(diǎn)的單核苷酸突變經(jīng)統(tǒng)計(jì)學(xué)分析得出p0.05具有統(tǒng)計(jì)學(xué)意義。該位點(diǎn)OR值為4.8331，多見于痙攣性斜頸組，提示該位點(diǎn)可能為痙攣性斜頸的危險(xiǎn)因素。 結(jié)論： 1.DRD5基因的ORF上1096、1199、1229、1268、1269位點(diǎn)無突變。 2.DRD5基因的ORF上877位點(diǎn)的單核苷酸位點(diǎn)的突變差異具有統(tǒng)計(jì)學(xué)意義，該位點(diǎn)可能與痙攣性斜頸有關(guān)，可能為痙攣性斜頸的危險(xiǎn)因素。
[Abstract]:Background: dystonia is associated with the disorder of neurotransmitters such as dopamine 5-hydroxytryptamine and acetylcholine. The pathogenesis of spastic torticollis may be related to the gene polymorphism of D5 receptor. The frequency of allele 4 was higher than that of control group. These results suggest that the mutation of D5 receptor may be a susceptible factor of spasmodic torticollis. The dysfunction of D5 receptor may affect the dopaminergic pathway in basal ganglia. It is suggested that the abnormal function of dopamine receptor may be associated with the pathogenesis of spastic torticollis. In previous studies, the relationship between dopamine D5 receptor gene polymorphism and spasmodic torticollis was studied. It was found that the mutation of single nucleotide locus on the ORF of the open reading frame of dopamine D5 receptor gene (D5) was 877 / 10961 / 1999 / 1229 / 1268 / 1269, which was statistically significant and might be related to susceptibility to spasmodic torticollis. Objective: to investigate whether the mutation of ORF in the DRD5 gene in the prespasmodic study of spasmodic torticollis is related to the pathogenesis of spasmodic torticollis, and to provide molecular biological basis for the diagnosis of spasmodic torticollis. Methods: according to the mutation difference of single nucleotide locus on ORF, which was found in the previous study of spasmodic torticollis patients, there was a single nucleotide locus mutation at the locus 877, 1096, 1999, 1229, 1268, 1269, and the inner and outer primers were designed in the peripheral region of 6 loci. After nested PCR amplification, the target gene was sequenced directly to determine the point mutation of the gene in each sample. Results: a single nucleotide mutation was found in the ORF of DRD5 gene by gene sequencing. The mutation from A to G was consistent with the results of previous studies. The single nucleotide mutation at locus 109611991229C12681269 and locus 877 on ORF was statistically significant by statistical analysis. The OR value of the locus was 4.8331.It was more common in spasmodic torticollis group. These results suggest that this locus may be a risk factor for spasmodic torticollis. Conclusion:. 1. There was no mutation in the ORF of DRD5 gene. 2. The mutation of single nucleotide locus at locus 877 in ORF of DRD5 gene was statistically significant, which may be related to spasmodic torticollis and may be a risk factor for spasmodic torticollis.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R741

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

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2 吳逸雯;陳生弟;;肌張力障礙遺傳學(xué)發(fā)病機(jī)制及診斷策略[J];中國(guó)現(xiàn)代神經(jīng)疾病雜志;2013年07期

本文編號(hào)：1556585