朝鲜族、鄂伦春族醇代谢酶基因多态性与酒依赖的研究

目的了解醇脱氢酶（ＡＤＨ）和醛脱氢酶（ＡＬＤＨ）基因多态性与朝鲜族和鄂伦春族酒依赖发病的相互关系。方法采用耳血聚合酶链反应及等位基因特异性寡核苷酸杂交方法，检测ＡＤＨ和ＡＬＤＨ基因型在酒依赖患者（朝鲜族５５例，鄂伦春族３１例）与正常对照者（朝鲜族５０名，鄂伦春族３７名）人群中的分布频率。结果在酒依赖组与正常对照组之间，朝鲜族仅ＡＬＤＨ２基因频率的分布差异有非常显著性（Ｐ＜０．０１），而鄂伦春族的ＡＤＨ３基因频率分布和ＡＬＤＨ２基因频率分布的差异有非常显著性和显著性（Ｐ＜０．０１，Ｐ＜０．０５），两个民族的ＡＤＨ２基因频率分布差异均无显著性。结论提示朝鲜族酒依赖的发生与ＡＬＤＨ２基因有关，鄂伦春族则为ＡＬＤＨ２和ＡＤＨ３基因共同影响酒依赖的发生。     

汉族酒依赖高发家系醇醛脱氢酶基因多态性的对照研究

目的 了解醛脱氢酶ＡＬＤＨ２和醇脱氢酶ＡＤＨ２、ＡＤＨ３基因多态性在中国汉族酒依赖高发家系中的分布特点，研究其对酒依赖发病的影响作用。方法 采用美国酒精中毒遗传学研究协作组织提供的半定式酒精中毒评定量表，以９个汉族酒依赖高发家系４９个成年人体（酒依赖者２３例）及与酒依赖高发家系相配对的８个正常对象，采用ＤＮＡ扩增结合等位基因特异性寡核苷酸探针杂交方法，对样本进行ＡＤＨ２、ＡＤＨ３和ＡＬＤＨ２基因多     

阿尔茨海默病患者早老素-1基因内含子多态性分布的研究

目的 探讨早老素－１（ＰＳ－１）基因第８外显子３’端内含子等位基因多态性在散发性阿尔茨海默病（ＳＡＤ）发病机制中的作用。方法 应用聚合酶链反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）方法检测７５例ＳＡＤ患者（ＳＡＤ组）和７３例正常老年人（对照组）的ＰＳ－１基因第８外显子３’端内含子等位基因多态性分布。结果 ＳＡＤ组１等位基因频率明显高于对照组（Ｐ〈０．０１,ＲＲ＝１．８３）,２等位基因频率明显低于对照组（Ｐ〈０．０１,ＲＲ＝０．５５）;ＳＡＤ组２／２基因型频率低于对照组（Ｐ〈０．０５,ＲＲ＝０．３２）。结论 ＰＳ－１基因多态性与ＳＡＤ发病有关,ＳＡＤ发病与ＰＳ－１基因２等位基因呈明显负关联,与１等位基因呈明显正关联。ＰＳ－１基因２等位基因对ＳＡＤ发病可能有保护作用,１等位基因可能是ＳＡＤ发病的危险因素之一。     

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。     

血管性痴呆和脑梗塞患者载脂蛋白E基因多态性的分析比较

目的探讨ＡＰＯＥ多态性与血管性痴呆（ＶＤ）和脑梗塞（ＣＩ）的关系。方法应用ＰＣＲ－ＲＦＬＰ技术分析２０例ＶＤ、２４例ＣＩ及２４例健康老年人的ＡＰＯＥ基因型。结果ＶＤ和ＣＩ患者ε３频率均降低（Ｐ＜０．０５），ε４频率均升高（Ｐ＜０．０５），而两组患者间各等位基因频率差异均无统计学意义（Ｐ＞０．０５）；且ε４与血清ＡＰＯＥ、ＡＰＯＢ、ＴＣ、ＬＤＬ－Ｃ正相关，与ＡＰＯＡ、ＨＤＬ－Ｃ负相关。结论ＡＰＯＥ多态性与ＶＤ和ＣＩ的发病机制有关，其在这两种疾病中的作用可能相似。     

血管性痴呆患者载脂蛋白E基因多态性分析

目的：探讨我脂蛋白Ｅ（ＡｐｏＥ）基因多态性与血管性痴呆的关系。方法：应用免疫银光比色法分析１７例ＶＤ患者及２２例非痴呆患者的ＡｐｏＥ基因型。结果：ＶＤ组ε４基因频率明显高于对照组（Ｐ＜０．０１）,ε３频率降低（Ｐ＜０．０５）,且ε４与血清ＴＣ,ＬＤＬ－Ｃ呈正相关,与ＨＤＬ－Ｃ负相关。结论：ε４可能是ＶＤ的危险因子,其机制可能与大脑血管的变性和损害有关。     

缺血性脑卒中患者红细胞膜脂质、微粘度及血清脂质分析

对５３例缺血性脑卒中（ＩＳ）患者红细胞膜胆固醇（膜ＣＨ）、膜磷脂（膜ＰＬ）、膜微粘度（膜）及血清脂质进行测定，并与４１例对照组相比。结果显示：①ＩＳ患者膜ＣＨ、膜ＣＨ与膜ＰＬ比值（膜ＣＨ／膜Ｐｕ及膜显著增高（Ｐ＜０．０１），膜亏与膜ＣＨ及膜ＣＨ／膜ＰＬ呈显著正相关；②ＩＳ组血清胆固醇（ＣＨ）、载脂蛋白Ｂ（ＡＰＯ－Ｂ）均显著增高（Ｐ＜０．０１），高密度脂蛋白胆固醇（ＨＤＬ－ＣＨ）和载脂蛋白Ａ＿１（ＡＰＯ－Ａ＿１）显著降低（Ｐ＜０．０１），膜ＣＨ和膜与ＡＰＯ－Ｂ呈显著正相关，而与ＨＤＬ－ＣＨ、ＡＰＯＡ＿１呈显著负相关。     

脑梗死急性期患者脑脊液LDH同功酶分析

的探讨脑梗死患者急性期脑脊液ＬＤＨ同功酶活性变化及其临床意义。方法脑梗死急性期患者３１例，对照组１８例，以琼脂糖凝胶电泳法检测脑脊液ＬＤＨ同功酶。结果脑梗死组与对照组比较ＬＤＨ１同功酶升高有显著差异（Ｐ＜００１），皮层动脉梗死组与腔隙性梗死组比较ＬＤＨ１同功酶升高有显著性差异（Ｐ＜００１），腔隙性梗死组与对照组比较ＬＤＨ１同功酶升高有显著差异（Ｐ＜００１）。结论脑梗死急性期脑脊液ＬＤＨ１同功酶活性增高，并与梗死体积大小、部位有关，对早期诊断及预后判断有重要价值。     

急性脑血管病时心肌酶谱的变化

目的　观察急性脑血管病时心肌酶的变化。方法　对７８例急性脑血管病患者和３６例健康查体者静 脉血清ＧＯＴ、ＬＤＨ、ＣＫ、α－ＨＢＤＨ于发病３天内进行检测。结果　血清ＧＯＴ、ＬＤＨ、ＣＫ、α－ＨＢＤＨ水平急性脑血管 病组明显高于对照组（Ｐ＜０．０１）,而脑出血组与脑梗死组患者之间心肌酶水平无明显差异（Ｐ＜０．０５）,有意识障碍 与无意识障碍患者血清ＧＯＴ、ＬＤＨ、α－ＨＢＤＨ有显著性差异（Ｐ＜０．０５）,ＣＫ有非常显著性差异（Ｐ＜０．０１）。结论 急性脑血管患者有心肌酶谱的变化,其程度与病变范围及意识障碍程度相一致,与病变的性质无关。     

多稀康对缺血性脑血管病患者血清高密度脂蛋白及其亚组分的影响

对３５例脑血栓形成患者在口服多烯康前后测定其血清ＨＤＬ－Ｃ及其亚组分改变。治疗前病人血清ＨＤＬ－Ｃ，ＨＤＬ２－Ｃ，ＨＤＬ２－Ｃ／ＨＤＬ３－Ｃ均明显低于对照组（Ｐ＜０．０１）。服用４周多烯康后，ＨＤＬ－Ｃ浓度升高，但无统计学意义，而ＨＤＬ亚组分发生了明显改变，ＨＤＬ２－Ｃ浓度升高，ＨＤＬ２－Ｃ／ＨＤＬ３－Ｃ比值升高，与治疗前相比均具有显著差异（Ｐ＜０．０１，Ｐ＜０．０５）。ＨＤＬ－Ｃ，ＨＤＬ３－Ｃ治疗前后无明显改变。提示：多烯康可提高ＨＤＬ特别对ＨＤＬ２－Ｃ的作用较明显。     

汉族酒依赖高发家系单胺氧化酶A基因多态性的对照研究

目的 了解单胺氧化酶Ａ（ＭＡＯＡ）基因多态性在汉族酒依赖高发家系和对照家系中的分布特点及对酒哪病的影响。方法 采用美国酒依赖遗传研究协作组的半定式酒依赖遗传量表,按入组标准筛选出９个酒依赖高发家系４９名成年个体（其中有酒依赖患者２３例）及８个对家系４５名成年个体。采用多聚酶链式反应和限制性片段长度多态性ＥｃｏＲＶ酶切法检测ＭＡＯＡ基因。结果 酒依赖高发家系与对照家系间ＭＡＯＡ等位基因频率差异有非常     

Protective association of genetic variation in alcohol dehydrogenase with alcohol dependence in Native American Mission Indians

OBJECTIVE: Two alcohol dehydrogenase genes (ADH2 and ADH3 on chromosome 4) and one aldehyde dehydrogenase gene (ALDH2 on chromosome 12) exhibit functional polymorphisms. The goal of this study was to determine whether any associations exist between the ADH2, ADH3, and ALDH2 polymorphisms and alcohol dependence in a group of Native Americans. An additional goal was to determine if any associations exist between these polymorphisms and the endophenotype, maximum number of drinks ever consumed in a 24-hour period. METHOD: Mission Indian adults (N=340) were recruited for participation from reservations in southern California. Each participant completed an interview with the Semi-Structured Assessment for the Genetics of Alcoholism. A blood sample was collected from each participant for genotyping at the ALDH2, ADH2, and ADH3 loci. RESULTS: Sixty percent of all participants (72% of men and 53% of women) met lifetime DSM-III-R criteria for alcohol dependence. A significant difference in the ADH2 allele distributions was found between alcohol-dependent and non-alcohol-dependent participants. Those with alcohol dependence were significantly less likely to have the ADH2*3 allele (odds ratio=0.28) and significantly more likely to have the ADH2*1 allele (odds ratio=2.00) than those who were not alcohol dependent. Individuals with ADH2*3 reported a lower number of maximum drinks ever consumed in a 24-hour period, compared to those without this allele. CONCLUSIONS: These results are consistent with genetic linkage studies showing protective associations for alcohol dependence and related behavior on chromosome 4 and suggest that ADH2 polymorphisms may account for these findings. These results also highlight the utility of evaluating protective factors in populations with high rates of alcohol dependence.     

乙醇脱氢酶1C 基因多态性与中国北方汉族男性酒精依赖的关联

目的：分析中国北方汉族男性乙醇脱氢酶1C（ADH1C）基因多态性与酒精依赖的关联。方法选取60例符合DSM －Ⅳ诊断标准的中国北方汉族男性酒精依赖患者及60名与之匹配的健康志愿者,测定其ADH1C基因上rs698位点的多态性,对酒精依赖组及健康对照组间各基因型和等位基因频率分布的差异进行比较。结果酒精依赖组患者的基因型分别为AA型32例,AG型27例,GG型1例,健康对照组AA型27人,AG型30人,GG型3人,两组间基因型和等位基因频率分布的差异无统计学意义（P＞0．05）。结论中国北方汉族男性ADH1C基因rs698位点多态性与酒精依赖无关联。     

Alcohol and aldehyde dehydrogenase polymorphisms in men with type I and Type II alcoholism

OBJECTIVE: The authors examined the genetic polymorphisms of alcohol dehydrogenase 2 and 3 (ADH2 and ADH3) and aldehyde dehydrogenase (ALDH2) in patients diagnosed as having Cloninger's type I or type II alcoholism. METHOD: Seventy-two alcoholic men and 38 nonalcoholic, healthy men were tested for the distribution of genotypes and alleles of ADH2, ADH3, and ALDH2. Forty-eight of the alcoholic men had type I alcoholism, and 24 had type II alcoholism. RESULTS: The frequencies of ADH2*1 and ADH3*2 alleles were significantly higher in men with type II alcoholism than in men with type I alcoholism and healthy men. The frequency of the ALDH2*1 allele was significantly higher in men with alcohol dependence than in healthy men. CONCLUSIONS: The genetic characteristics of alcohol dehydrogenases in men with type I alcoholism were similar to those of healthy men, and the genetic characteristics of aldehyde dehydrogenase in men with type I alcoholism were similar to those of men with type II alcoholism. These findings suggest that the genetic characteristics of alcohol metabolism in type I alcoholism fall between nonalcoholism and type II alcoholism.     

D2 dopamine receptor and alcohol dehydrogenase 2 genes with Polynesian alcoholicsAssociation of D2 dopamine receptor and alcohol dehydrogenase 2 genes with Polynesian alcoholics

Alleles of the D2 dopamine receptor (DRD2) and the alcohol dehydrogenase 2 (ADH2) genes were determined in 69 French Polynesian alcoholic patients and 57 controls matched for racial origin. Three racial groups were studied: pure Polynesians (PP), Polynesians mixed with Caucasian (PCA) ancestry and Polynesians mixed with Chinese (PCH) ancestry. DRD2 A1 allele frequencies in the alcoholics compared to their controls in these groups were: PP, .26 vs .32 (P = .69); PCA, .44 vs .35 (P = .46); PCH, .40 vs 0.39 (P = .88). ADH2 1 allele frequencies in alcoholics compared to their controls groups were: PP, .56 vs .62 (P = .66); PCA, .75 vs .56 (P = .09); PCH, .78 vs .32 (P = .009). In the PCA group, the combination of the DRD2 A1 genotypes and the ADH2 1 homozygotes was strongly associated with alcoholism (P = .0027). This preliminary study shows the importance of ascertaining racial ancestry in molecular genetic association studies. Moreover, it suggests that a combination of genes are involved in susceptibility to the development of alcoholism.     

酒精依赖甲基化敏感基因筛选

目的 探讨候选基因甲基化状态和酒精依赖之间的关联,初步了解表观遗传在酒精依赖病理机制中的作用和意义.方法 运用全基因组甲基化芯片,对63例酒精依赖者(酒精依赖组)及65名年龄、文化程度、地域相匹配的健康对照者(对照组)进行检测和分析.结果 2组基因乙醇脱氢酶1A(ADH1A)、乙醛脱氢酶3B2(ALDH3B2)、5-羟...     

Association of a polymorphism of the serotonin 1B receptor gene and alcohol dependence with inactive aldehyde dehydrogenase-2

Summary. The use of persons who become alcoholic despite having a well-defined negative risk for alcoholism (inactive aldehyde dehydrogenase-2 or ALDH2) is advantageous in genetic research because of this population's reduced heterogeneity and possible genetic factors conferring susceptibility to alcohol dependence. This investigation of central serotonin neurotransmission, specifically the serotonin 1B (5HT1B) receptor gene and its role in both regulating alcohol consumption and developing alcohol dependence revealed overrepresentation of the C allele of the 861G>C polymorphism of 5HT1B in alcoholics with inactive ALDH2, compared with its frequency in nonalcoholic controls. No significant differences in 5HT1B genotype and allele distributions were observed between alcoholics with active ALDH2 and controls, however. Taken together with recent observations, these results suggest that genetic variability of the 5HT1B receptor is involved in the development of some type of alcohol dependence. Received October 10, 2001; accepted November 9, 2001     

Alcohol abuse and related factors in Asia

Alcohol problems are a global issue, and the nature of alcohol abuse is very complicated. The susceptibility to alcohol abuse varies greatly from one individual to another and also from one nation to another, depending on the availability of alcohol, a country's regulation related to alcohol, a country's cultural background, religious tradition and its economics. Alcohol dependence is also a complicated disease process. The prevalence of alcohol dependence also varies greatly from one ethnic group to another. Asia is the world's largest and most populous continent. The natural disasters, religious conflicts as well as political disputes cause people lack of opportunity in many countries. People in this region do not consume more alcohol than the people in the rest of the world. The prevalence of alcohol dependence is not as high as is seen in other regions. In Asia, not only socio-economic factors, but also biological factors influence drinking behaviour. Findings of functional genetic polymorphism of the major alcohol metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) have led to the suggestion that this enzyme system may possibly play a diverse but critical role in alcohol dependence and in the alcohol-related disease process in the different ethnic groups. This paper reviews alcohol problems and related factors. Their management and prevention strategy are discussed.     

Association of a polymorphism of the 5HT2A receptor gene promoter region with alcohol dependence

Approximately 10% of Japanese alcoholics develop their disease despite having an inactive form of aldehyde dehydrogenase-2 (ALDH2), known as a genetic deterrent of heavy drinking due to adverse reactions after drinking. Such alcoholics are considered to be advantageous in genetic research because they should show reduced heterogeneity and possess genetic factors conferring susceptibility to alcohol dependence. Examination of the -1438 A/G polymorphism of the serotonin 2A (5HT2A) receptor gene in 225 Japanese alcoholics with inactive ALDH2 revealed the presence of significantly more of the G allele than was found in 361 control subjects. The frequency of the G allele in 282 alcoholics with active ALDH2 fell between the G allele frequencies of controls and subjects with inactive ALDH2. These data suggest that although the effect is relatively small, genetic variability in the 5HT2A receptor is involved in the development of alcohol dependence.