【摘要】：目的：系統(tǒng)的檢測(cè)中國(guó)漢族帕金森病(Parkinson's disease, PD)患者ATP1B4(the ATPase Na+/K+transporting beta4polypeptide gene)基因全部編碼區(qū)的所有變異,分析這些變異的基因型和等位基因頻率在中國(guó)漢族PD患者組和正常對(duì)照組之間分布是否有差異,明確ATP1B4與中國(guó)漢族PD發(fā)病的相關(guān)性。 方法：首先對(duì)100例PD患者的ATP1B4基因全部編碼區(qū)及部分非編碼區(qū)用聚合酶鏈?zhǔn)椒磻?yīng)-單鏈構(gòu)象多態(tài)性(Polymerase chain reaction-single strand conformation polymorphism, PCR-SSCP)結(jié)合測(cè)序的方法進(jìn)行篩查并確定變異類(lèi)型。然后用統(tǒng)計(jì)學(xué)方法分析已發(fā)現(xiàn)變異的基因型與等位基因頻率在202例PD患者組及400例與患者匹配的正常對(duì)照組間的分布差異。 結(jié)果：由于ATP1B4基因位于X染色體上,統(tǒng)計(jì)學(xué)分析時(shí)將男女分開(kāi)統(tǒng)計(jì)。篩查100例PD患者發(fā)現(xiàn)一個(gè)變異rs2072452(c.143TC),統(tǒng)計(jì)學(xué)分析發(fā)現(xiàn)該變異的基因頻率、等位基因頻率在100例女性PD患者和200例女性對(duì)照間,102例男性患者和200例男性對(duì)照之間的分布均無(wú)統(tǒng)計(jì)學(xué)差異。 結(jié)論：ATP1B4基因編碼區(qū)的變異與中國(guó)漢族PD的發(fā)病無(wú)關(guān)。 目的：篩查中國(guó)漢族帕金森病(Parkinson's disease, PD)患者FBXO42(F-box protein42gene)基因全部編碼區(qū)的所有變異,分析中國(guó)漢族PD患者組和正常對(duì)照組之間這些變異的基因頻率和等位基因頻率分布是否有差異,確定FBXO42與中國(guó)漢族PD發(fā)病的相關(guān)性。 方法：首先對(duì)151例PD患者的FBXO42基因全部編碼區(qū)及部分非編碼區(qū)用聚合酶鏈?zhǔn)椒磻?yīng)-單鏈構(gòu)象多態(tài)性(Polymerase chain reaction-single strand conformation polymorphism, PCR-SSCP)結(jié)合測(cè)序的方法進(jìn)行篩查并確定變異類(lèi)型。然后用統(tǒng)計(jì)學(xué)方法分析已發(fā)現(xiàn)變異的基因頻率與等位基因頻率在316例PD患者(包括之前的151例)及295例與患者匹配(按性別,年齡及地域進(jìn)行匹配)的正常對(duì)照組間的分布差異,并對(duì)發(fā)現(xiàn)的多個(gè)變異進(jìn)行單體型分析。 結(jié)果：1.對(duì)FBXO42基因檢測(cè)發(fā)現(xiàn)患者組和對(duì)照組存在三個(gè)變異(rs2273311,rs12069239和rs35196193),此外,在一名散發(fā)PD患者中發(fā)現(xiàn)一個(gè)新的TC堿基替換c.1407TC。在線預(yù)測(cè)發(fā)現(xiàn)四個(gè)變異均不改變剪接位點(diǎn)。2.統(tǒng)計(jì)分析發(fā)現(xiàn)三個(gè)變異(rs2273311, rs12069239和rs35196193)的基因頻率及等位基因頻率在316例PD患者和295例正常對(duì)照之間的分布無(wú)統(tǒng)計(jì)學(xué)差異。3.單倍體分析發(fā)現(xiàn)FBXO42基因的 個(gè)常見(jiàn)單體型G-C-G (rs2273311-rs12069239-rs35196193)與中國(guó)漢族PD的發(fā)病相關(guān)(P=0.002, OR=1.69,95%CI=1.06-2.71),進(jìn)行Bonferroni校正后仍有統(tǒng)計(jì)學(xué)意義(P=0.008)。結(jié)論：雖然FBXO42基因的編碼區(qū)變異可能與中國(guó)漢族PD發(fā)病無(wú)關(guān),但FBXO42基因的單體型(G-C-G)可能使PD的發(fā)病風(fēng)險(xiǎn)增高。
[Abstract]:Objective: to detect all mutations of ATP1B4 (the ATPase Na / K transporting beta4polypeptide gene in Chinese Han patients with Parkinson's disease (Parkinson's disease, PD). To analyze the difference of genotype and allele frequency between Chinese Han PD patients and normal controls, and to determine the correlation between ATP1B4 and PD in Han nationality. Methods: all and part of the coding regions of ATP1B4 gene in 100 patients with PD were screened by polymerase chain reaction-single strand conformation polymorphism (SSCP) (Polymerase chain reaction-single strand conformation polymorphism, PCR-SSCP combined with sequencing and the type of variation was determined. The frequency of alleles and genotypes in 202 PD patients and 400 matched normal controls were analyzed by statistical method. Results: because the ATP1B4 gene was located on X chromosome, the male and female were separated by statistical analysis. A variant of rs2072452 (c.143TC) was found in the screening of 100 patients with PD. The allele frequency and allele frequency of the mutation were found in 100 female PD patients and 200 female controls by statistical analysis. There was no significant difference in distribution between 102 male patients and 200 male controls. Conclusion: the variation of ATP1B4 gene coding region is not related to the pathogenesis of PD in Han nationality. Objective: to screen all mutations in the whole coding region of FBXO42 (F-box protein42gene) gene in patients with Parkinson's disease (Parkinson's disease, PD) in Chinese Han nationality. To determine the relationship between FBXO42 and PD in Han nationality, we analyzed whether there were differences in the distribution of allele frequencies and gene frequencies between Chinese Han PD patients and normal controls. Methods: all and part of the coding regions of FBXO42 gene in 151 patients with PD were screened by polymerase chain reaction-single strand conformation polymorphism (SSCP) (Polymerase chain reaction-single strand conformation polymorphism, PCR-SSCP combined with sequencing and the type of variation was determined. Then statistical analysis was used to analyze the frequency of alleles and alleles found in 316 PD patients (including the previous 151 cases) and 295 matched patients (by sex). Age and region matching were used to analyze the distribution and haplotype of multiple variations found in normal controls. Results: 1. Three mutations (rs2273311,rs12069239 and rs35196193) were found in the FBXO42 gene group and the control group. In addition, a new TC base replacement c.1407TCwas found in a sporadic PD patient. Online prediction found that none of the four variants changed splicing sites. 2. 2. Statistical analysis showed that there was no significant difference in the distribution of gene frequencies and alleles between 316 PD patients and 295 normal controls (rs2273311, rs12069239 and rs35196193). Haploid analysis showed that G-C-G (rs2273311-rs12069239-rs35196193), a common haplotype of FBXO42 gene, was associated with PD in Han nationality (P0. 002, OR=1.69,95%CI=1.06-2.71). There was statistical significance after Bonferroni correction (P0. 008). Conclusion: although the variation of the coding region of FBXO42 gene may not be associated with the pathogenesis of PD in Chinese Han nationality, the haplotype (G-C-G) of FBXO42 gene may increase the risk of PD.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R742.5

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