细胞色素P450_2D_6基因Xba I 限制性片段长度多态性及点突变与帕金森病的关系

目的探讨机体的第Ｉ相解毒系统障碍与帕金森病（ＰＤ）遗传易患性的关系。方法选择ＰＤ病人１００例和正常人１００名，利用ＸｂａＩ限制性片段长度多态性（ＲＦＬＰ）和ＰＣＲＲＦＬＰ技术，检测细胞色素Ｐ４５０２Ｄ６（ＣＹＰ２Ｄ６）基因的突变。比较ＰＤ病人与正常人之间多态性频率的差异。结果ＸｂａＩＲＦＬＰ分析可见ＰＤ病人组４４ｋｂ等位基因频率，以及４４ｋｂ／４４ｋｂ纯合子的频率高于正常对照组，而且在病人组Ａ、Ｂ、Ｃ１８８→Ｔ、Ｃ４２６８→Ｃ、Ｃ２９３８→Ｔ点突变频率也高于正常对照组，使患ＰＤ的危险性提高，危险度达２０倍左右。结论解毒酶ＣＹＰ２Ｄ６基因突变增加患ＰＤ的危险性。这提示解毒酶缺陷可能是ＰＤ遗传易患性的重要原因。     

细胞色素P4502D6基因XbaⅠ限制性片段长度多态性及点突变与帕 …

目的探讨机体的第Ⅰ相解毒系统障碍与帕金森病遗传易患性的关系。方法 选择ＰＤ病人１００例和正常人１００名，利用ＸｂａⅠ限制性片段长度多态性和ＰＣＲ－ＲＦＬＰ技术，检测细胞色素Ｐ４５０２Ｄ６基因的突变。比较ＰＤ病人与正常人之间多态性频率的差异。结果 ＸｂａＩＲＦＬＰ分析可见ＰＤ病人组４４ｋｂ等位基因频率，以及４４ｋｂ／４４ｋｂ纯合子的频率高于正常对照组，而且在病人组，Ａ，Ｂ，Ｃ１８８→Ｔ，Ｃ４２６８→     

谷胱甘肽转移酶μ基因多态性与帕金森病的关系

目的为了研究机体解毒系统的障碍在帕金森病（ＰＤ）遗传易感性中的作用。方法选择确诊的ＰＤ病人和年龄、性别基本匹配的正常人各１００名，分离白细胞ＤＮＡ，利用聚合酶链反应检测解毒酶谷胱甘肽转移酶μ（ＧＳＴＭ）基因突变率，并分析比较ＰＤ病人与正常人之间多态性频率的差异。结果发现ＧＳＴＭ无效基因（ＧＳＴＭ０型）使患ＰＤ的危险性提高１５３倍。结论提示解毒酶ＧＳＴＭ０基因缺陷可能是ＰＤ遗传易感性的一个原因。     

儿茶酚胺氧位甲基转移酶基因多态性与帕金森病关系的探讨

目的 探讨儿茶酚胺氧位甲基转移酶（ＣＯＭＴ）基因Ｇ１９４７→Ａ位点突变所致的基因多态性与帕金森病（ＰＤ）遗传易患性的关系。方法 利用聚合酶链反应－限制性片和蔗多态性（ＰＣＲ－ＲＦＬＰ）技术分析了１０５例帕金森病患者与１１５名正常健康成人对照组ＣＯＭＴ的基因多态性位点频率。结果 ＰＤ组Ａ等位基因频率为２５．７％,而对照组为２６．５％,两组差异不显著。基因型分布频率在ＰＤ和对照组之间差异有显著意义（Ｐ     

脑动脉硬化的脑电图,脑电地形图经颅多普勒超声的对照研究

目的 探讨脑电图（ＥＥＧ）、脑电地形图（ＢＥＡＭ）及经颅多普勒超声（ＴＣＤ）三项检查联合应用对脑动脉硬化的诊断价值。方法 ２０８例临床诊断为脑动脉硬化的病人,均在发病一月内行ＥＥＧ、ＢＥＡＭ及ＴＣＤ检查。结果 ＥＥＧ异常７４例,ＢＥＡＭ异常１２５例住院ＴＣＤ异常率为１００％。ＥＥＧ与ＢＥＡＭ比较（Ｘ＾２＝２５．０６,Ｐ〈０．０１）。有非常显著差异;ＢＥＡＭ与ＴＣＤ比较（Ｘ＾２＝４．１２,Ｐ〈０．０     

依赖还原型辅酶Ⅰ/Ⅱ醌氧化还原酶基因多态性与帕金森病遗传易患性的关系

目的探讨依赖还原型辅酶Ⅰ／Ⅱ醌氧化还原酶基因ｃＤＮＡ６０９位碱基Ｃ→Ｔ点突变所致的基因多态性是否与帕金森病遗传易患性有关。方法采用聚合酶链反应限制性片段长度多态性（ＰＣＲＲＦＬＰ）的方法分析了１２６例帕金森病（ＰＤ）病人与１３６名健康成人对照组ＮＱＯ１的基因多态性。结果ＰＤ组的Ｔ等位基因频率为５２％,而对照组为４３％,两组差异有显著意义（Ｐ＜０．０５）。基因型分布在ＰＤ和对照组之间差异有显著意义（Ｐ＜０．０５）,带Ｔ等位基因的个体患ＰＤ的风险增加３．８倍。结论本研究结果提示ＮＱＯ１基因ｃＤＮＡ６０９突变Ｔ等位基因可能是ＰＤ发生的危险性因素,与ＰＤ的遗传易患性有关。     

强直性肌营养不良病人的三核苷酸数目的检测

目的　检测强直性肌营养不良（ Ｄ Ｍ ）病人的三核苷酸重复数目。方法　采用３２ Ｐ 标记的 Ｐ Ｃ Ｒ 和聚丙烯酰胺凝胶电泳技术，对 ３ 例 Ｄ Ｍ 病人的外周血和肌活检组织的 Ｃ Ｔ Ｇ 重复数目进行了分析。结果　３ 例 Ｄ Ｍ 病人 Ｃ Ｔ Ｇ 重复扩增片段分别为 １４６ｂｐ、１４９ｂｐ 和 １４９ｂｐ，相应的 Ｃ Ｔ Ｇ 重复数为 １１、１２、１２，其基因型为 １１／１１、１２／１２、１２／１２。结论　 Ｄ Ｍ 病人的 Ｃ Ｔ Ｇ 重复数目大多在 ５０～４０００ 不等，但是少数病人的 Ｃ Ｔ Ｇ 重复数目可在正常范围，一般认为是遗传异质性或基因突变所致。 Ｃ Ｔ Ｇ 重复数目正常的病人并不能排除 Ｄ Ｍ 的诊断。     

血清ApoE对脑动脉硬化症的诊断价值

本文观察４２例脑动脉硬化症患者与正常对照组４４例，对其血清ＡｐｏＥ和ＨＤＬ－Ｃ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡｐｏＡＩ、ＡｐｏＢ１００２６含量进行测定，并将ＡｐｏＥ与ＨＤＬ－Ｃ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡｐｏＡＩ、ＡｐｏＢ１００逐一进行相关比较，结果发现：脑动脉硬化症病人血清ＡｐｏＥ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡｐｏＢ１００明显高于正常对照组（Ｐ〈０．０１），ＨＤＬ－Ｃ显著低于正常对照组（Ｐ〈０．０１）     

载脂蛋白E与脑动脉硬化症

本文观察７８例脑动脉硬化症患者与对照组４４例，对其血清载脂蛋白Ｅ（ＡＰＯＥ）和高密度脂蛋白（ＨＤＬ－Ｃ）、低密度脂蛋白（ＬＤＬ－Ｃ）、胆固醇（ＴＣ）、甘油三脂（ＴＧ）、载脂蛋白ＡＩ（ＡＰＯＡＩ）、载脂蛋白Ｂ（１００）（ＡＰＯＢ（１００））进行含量测定，并将ＡＰＯＥ与ＨＤＬ－Ｃ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡＰＯＡＩ、ＡＰＯＢ（１００）逐一进行相关比较，结果发现：脑动脉硬化症病人（ＣＡＳ）血清ＡＰＯＥ、ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡＰＯＢ（１００）明显高于正常对照组（Ｐ＜０．０１），ＨＤＬ－Ｃ显著低于正常对照组（Ｐ＜０．０１），ＡＰＯＡＩ无明显变化（Ｐ＞０．０５），且ＡＰＯＥ与ＨＤＬ－Ｃ呈负相关；与ＬＤＬ－Ｃ、ＴＣ、ＴＧ、ＡＰＯＢ（１００）呈正相关；与ＡＰＯＡＩ无直线相关关系。提示ＡＰＯＥ可做为诊断脑动脉硬化症的重要指标。     

脑出血与8项血脂指标的关系探讨

测定了１２５例脑出血病人的血总胆固醇（ＴＣ）、甘油三酯（ＴＧ）、高密度脂蛋白（ＨＤＬ）、低密度脂蛋白（ＬＤＬ）、载脂蛋白Ａ－１、Ｂ－１００（ＡｐｏＡ－１、ＡｐｏＢ－１００）、脂蛋白（ａ）［ＬＰ（ａ）］和氧化修饰低密度脂蛋白（ｏｘＬＤＬ）浓度。结果显示：与对照组比较，ＡｐｏＢ－１００、ｏｘＬＤＬ显著增高，ＨＤＬ、ＡｐｏＡ－１显著降低（Ｐ＜０．０１），ＬＤＬ明显降低（Ｐ＜０．０５），ＴＣ、ＴＧ、ＬＰ（ａ）无明显变化（Ｐ＞０．０５）。提示：血ＬＤＬ、ＡｐｏＢ－１００、ｏｘＬＤＬ浓度增高和ＨＤＬ、ＡｐｏＡ－１浓度降低与脑出血有一定的相关关系，可作为脑出血的危险因素。     

Frequency of CYP2D6 allelic variants in multiple sclerosis

Recent reports have shown association between CYP2D6 polymorphism and neuronal degenerative diseases such as Parkinson's disease. We investigated the association between this polymorphism and the risk for developing multiple sclerosis (MS). Leucocyte DNA from 118 MS patients and a control group of 200 unrelated healthy individuals was studied for the occurrence of 8 different CYP2D6 allelic variants by using allele-specific PCR amplification, Xba I and EcoR I RFLP analyses. The frequencies for these allelic variants in the MS and control groups were, respectively: CYP2D6wt 75.0% and 79.3%, CYP2D6A 0.4% and 1.3%, CYP2D6B 11.4% and 12.0%, CYP2D6C 4.2% and 2.0%, CYP2D6D 3.0% and 2.3%, CYP2D6L 0.8% and 0.3%, CYP2D6L2 5.1% and 3.0%. The frequencies of subjects with high CYP2D6 activity (those carrying two or more functional genes) were 77.1% and 73.5% in MS and control groups. The frequencies of subjects with absent CYP2D6 activity (those lacking functional genes) were 3.4% and 4.5% in MS and control groups, respectively. These results indicate that mutations at the CYP2D6 gene do not seem to be a factor in determining susceptibility to MS.     

Mitochondrial NADH dehydrogenase and CYP2D6 genotypes in Lewy-body Parkinsonism

The cause of nerve-cell death in sporadic Parkinson's disease remains unknown. Although environmental factors have been traditionally implicated in the etiology of Parkinson's disease, recent studies strongly suggest that there is a genetic contribution to this multifactorial disorder. We studied archival brain tissue from clinically and neuropathologically verified cases of Parkinson's disease, using nonradioactive cycle sequencing and restriction enzymatic analysis of polymerase chain reaction products. Twenty-one Parkinsonian brains with brain stem Lewy-bodies and 77 control brains were genotyped at two mitochondrial loci previously implicated in the etiology of neurodegenerative disease. In addition, genotyping was performed for two alleles of the debrisoquine 4-hydroxylase gene (CYP2D6). A heteroplasmic mtDNA^G5460A missense mutation in the ND2 subunit gene of NADH dehydrogenase was three times more frequent in Parkinson cases (4/21) compared to controls (5/77). A homoplasmic mtDNA^A4336G transition which alters the mitochondrial tRNA^Gln gene product was found in one Parkinson case. Frequencies of the CYP2D6^G1934A and CYP2D6^C2938T alleles were not significantly different between Parkinson cases and controls. Two Parkinsonian brains with high degrees of heteroplasmy for the ND2^G5460A mutation and one CYP2D6^C2938T homozygous case showed very high numbers of Lewy-bodies in the substantia nigra. The results of this study are in line with the concept that different genetic loci may be involved in Parkinson's disease susceptibility. They provide a hint that the ND2⁵⁴⁶⁰ mutation, in combination with other factors, could play a role in disease pathogenesis in a subset of patients. © 1996 Wiley-Liss, Inc.     

The HhaI polymorphism in the CYP2D6 gene is not associated with Parkinson's disease in a Caucasian population

Polymorphisms of the CYP2D6 gene have been reported in association with susceptibility to Parkinson's disease (PD). In a Japanese population, a HhaI polymorphism in the CYP2D6 gene was associated with a 5.56-fold risk of PD (Tsuneoka et al., 1993). We investigated the frequency of this polymorphism in Caucasian patients with sporadic PD and in healthy controls. Although the frequency of the polymorphism was significantly higher in Caucasians compared with Japanese, there was no association with PD.     

Debrisoquine hydroxylase gene polymorphism in familial Parkinson''s disease.

Recent molecular genetic studies of the cytochrome P-450 system enzyme CYP2D6, which hydroxylates debrisoquine, have indicated an excess of mutant alleles in patients with Parkinson's disease compared with controls. This indicates that the CYP2D6 locus confers genetic susceptibility to Parkinson's disease. CYP2D6 polymorphism has been investigated in 48 patients with familial Parkinson's disease, from 22 families, and 88 of their unaffected relatives. An excess of CYP2D6 mutant alleles in patients compared with healthy relatives was found only in subjects over the age of 60 years, presumably reflecting the age related prevalence of this disease. There was no difference in distribution of genotypes, however, between sib pairs concordant or discordant for Parkinson's disease. Linkage analysis, exclusively with affected family members, yielded negative lod scores. These data indicate that the CYP2D6 locus is not the major determinant of genetic susceptibility in familial Parkinson's disease.     

CYP2E1基因5''侧翼区多态性与男性罹患ALS相关性推测

目的分析CYP2E1 5'侧翼区的Pst Ⅰ/Rsa Ⅰ多态性,探讨该多态性与散发性肌萎缩侧索硬化(SALS)遗传易感性的关系.方法利用PCR-RFLP的方法,对104例SALS患者及性别与年龄匹配的242例正常对照行基因多态性分析.结果SALS患者的c1c2杂合子和c2等位基因的频率比对照组有增高趋势,但统计学上均无显著性差异.将研究对象按性别分组后,c1c2杂合子的频率在男性患者中比对照组有显著性差异.随着诊断信度的提高,2个及以上区域的运动神经元受损的男性肌萎缩侧索硬化(ALS)患者,其c1c2杂合子的频率有了进一步的统计学差异.结论c2等位基因可能是男性罹患ALS的一个危险因素.SALS的发病与CYP2E1多态性导致的内源性增毒及其原位损伤可能有关.     

CYP2D6 polymorphism and Parkinson's disease susceptibility.

Following the recent identification of multiple novel mutations and alleles of the cytochrome P450 CYP2D6 gene which cause decreased, increased, or absent enzyme activity, we re-examined the controversial hypothesis of a role of the CYP2D6 polymorphism in Parkinson's disease (PD) susceptibility. For this purpose, a strategy based on PCR-SSCP and RFLP analyses allowing the detection of all known CYP2D6 alleles was performed in DNA from 109 patients with sporadic PD. This strategy was also applied to DNA from 68 members of PD families including 18 affected and 50 unaffected members. Seventeen mutations occurring alone or in various combination on 14 alleles of CYP2D6 have been identified in patients with sporadic PD. Moreover, 12 mutations and nine alleles of the gene have been characterized in members of PD families. No significant difference was observed when the distribution of mutations and alleles of CYP2D6 was compared between the PD patients and 514 control subjects previously analyzed using the same strategy. There was also no difference in the distribution of phenotypes predicted from genotypes between both groups. In addition, when the distribution of CYP2D6 genotypes was compared, no difference between affected and unaffected members of PD families was observed. These data indicate that CYP2D6 polymorphism is not a susceptibility factor to PD.     

难治性精神分裂症与细胞色素P4502D6基因多态性相关性研究

目的 探测难治性精神分裂症与细胞色素P4502D6基因多态性关系。方法 用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术分析92例难治性精神分裂症患者的CYP2D6基因多态性,并以92例正常人作为对照。结果 在难治性精神分裂症组和对照组中,等位基因C、T及基因型T/T的差异具有非常显著性和显著性（P=0.002;P=0.002;P=0.014）。结论 本组样本中CYP2D6C188T基因多态性与难治性精神分裂症关联。提示CYP2D6C188T突变可能是难治性精神分裂症发病因素之一,本组中国汉族人中22号染色体长臂（22q13.1）可能存在难治性精神分裂症易感性基因。     

No evidence of an association between CYP2D6 polymorphisms among Japanese and dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most frequent degenerative dementia among the elderly, following Alzheimer-type dementia (ATD). An association of DLB with CYP2D6*4, one of the cytochrome P450IID6 (debrisoquine 4-hydroxylase; CYP2D6) gene polymorphisms, was reported previously, but this is controversial. Moreover, these reports have been restricted to Caucasian populations. Therefore, we compared frequencies of CYP2D6*3, *4, and *10 mutant alleles in 17 Japanese DLB patients to those among Alzheimer-type dementia (ATD) patients and healthy controls. Polymerase chain reaction amplification and restriction fragment length polymorphism analyses were used for genotyping. No significant difference of genotype or mutant allele frequencies was detected between DLB, ATD, and healthy controls. The present results do not support the suggestion that the CYP2D6 gene is related to DLB susceptibility, at least in the Japanese population.     

miR146a基因多态性与早发型阿尔茨海默病的关联性研究

目的 探讨miR146a的基因多态性与早发型阿尔茨海默病（EOAD）的关系.方法 本研究共纳入103例EOAD患者和100名健康对照组人群,采用SnapShot分型技术检测miR146a基因的rs2910164和rs57095329的多态性.结果 病例组的rs57095329位点的基因型和等位基因频率与健康对照组比较,差异有统计学意义（基因型P=0.027 0,等位基因频率P=0.004 2）,而rs2910164的病例组和对照组基因型和基因频率差异无统计学意义（基因型P=0.595 7,等位基因频率P=0.322 6）.结论 miR146a基因的rs57095329多态位点与EOAD的发病风险具有相关性,rs57095329的G等位基因是EOAD的发病风险的保护因素.