汉族健康人201名的酒精代谢相关酶基因多态型分布

目的 了解乙醇脱氢酶2(ADH2)基因型和乙醛脱氢酶2(ALDH2)基因型的分布情况,为筛选高危敏感个体和采取预防措施以减少酒精相关性疾病的发生提供理论基础。方法 问卷调查筛选出居住在四川省的无直接血缘关系的汉族健康个体201人(男104人,女97人)、采集血样并搜集饮酒行为资料;聚合酶链式反应．限制性片段长度多态性方法测定ADH2、ALDH2基因型。结果 杂合型ADH2与纯合型ALDH2在中国汉族正常人口中占优势(分别为53．23％,68．16％);9种ADH2、ALDH2基因型组合的分布间差异无统计学意义;纯合型ALDH2在具高、中饮酒频率男性中的分布间差异有统计学意义。结论 汉族正常人口中携带酒精相关性疾病易感基因型个体占多数(68．16％),应加强监测与预防酒精相关性疾病的工作。     

中国汉坦病毒基因型及分布

汉坦病毒（Hantavirus,HV）属于布尼亚病毒科（Bunyaviridae）汉坦病毒属（genus hantavirus）。HV是人类疾病的重要病原体,人类感染HV后主要导致2种严重疾病,即肾综合征出血热（hemorrhagic fever withrenal syndrome,HFRS）和汉坦病毒肺综合征（hantavirus pulmonary syndrome,HPS）。近几年HV的研究进展较快,世界HV分布区不断扩大,     

中国不同卵性类型双生子出生率的地区分布

目的 探讨中国不同卵性类型双生子出生率的地区分布特点.方法 选用全国各省市区1989年全年出生的双生子数据,用Weinberg差别法对双生子进行卵性分类.结果 MZ和DZ双生子出生率水平与地理区域性有关,且两者具有不同的地区分布模式.结论 地区因素影响中国不同卵性类型双生子出生率.     

安徽省丙型肝炎病毒基因型分布

应用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）和限制性片段长度多态性（ＲＦＬＰ）技术分析安徽省丙肝患者丙型肝炎病毒（ＨＣＶ）基因型。结果表明ＨＣＶ基因型有Ⅰ、Ⅱ、Ⅲ、Ⅳ及Ⅱ／Ⅲ混合型，以Ⅱ型感染（７５．６６％）占优势，其次为Ⅲ型（１３．２３％）和Ⅱ／Ⅲ型（６．３５％），Ⅰ、Ⅳ型各有１例（０．５３％）。安徽省北部地区的ＨＣＶⅢ型多于南部，而Ⅱ型北部则少于南部，不同地理区域ＨＣＶ基因型分布差异有显著性（Ｐ＜０．０５）。有、无输血、血液制品史的丙肝患者间ＨＣＶ基因型分布差异无显著性     

中国五个民族人群样本中酒精代谢相关酶基因多态型分布比较

采用聚合酶链式反应 限制性片段长度多态性 (PCR RFLP)方法测定酒精脱氢酶 2 (ADH2 )和乙醛脱氢酶 2 (ALDH2 )的基因型 ,以获得ADH2、ALDH2基因多态型在中国汉、回、蒙古、维吾尔、白五个民族正常人群样本中的分布并对其进行比较。结果显示 :(1)五民族中均为杂合型ADH2与纯合型ALDH2占优势 ;(2 )ADH2、ALDH2基因型在五民族的分布间存在一定差异     

酒精代谢酶基因多态性与酒精性肝病关系研究探讨

目的观察探讨酒精代谢酶基因多态性与酒精性肝病关系。方法选取我院2008年12月至2010年12月诊断为酒精性肝病（ALD）的患者50例,设为观察组A,选择有酗酒史的人群120例,设为观察组B;再选择同期体检健康的人群120名,设为对照组,观察比较3组人群酒精代谢酶基因的细胞色素P4502E1（CYP2E1）、乙醛脱氢酶2（ALDH2）、乙醇脱氢酶3（ADH3）的基因型及基因频率。结果 ALDH2的3种基因型在观察组A、B和对照组间分布比较皆存在一定差异（P〈0.05）,具有统计学意义。ALDH2的2种等位基因在观察组A、B与对照组间的分布比较存在一定差异（P〈0.05）,具有统计学意义。结论酒精代谢酶基因多态性与酒精性肝病的发生及发展有密切的关系,CYP2E1、ALDH2和ADH3均与酒精依赖有密切的关系意义。     

中国丙型肝炎病毒基因型分布

目的分析中国丙型肝炎病毒(HCV)基因型的分布及变化趋势。方法计算机检索1994年以来中国医院知识库(CHKD),1998年以来万方数据资源系统、中国生物医学文献数据库(CBMDisc)以及PubMed数据库,并结合文献追溯方法,收集国内HCV基因分型的相关文献。相同HCV亚型分别按地区、研究时间、人群分组,并进行简单数量合并,计算百分比。结果共纳人文献140篇(共168条记录)。不同地区HCV基因型存在差异,其中北方地区基因型较单一,以1b和2a型为主;南方地区HCV基因型种类较多,以1b型为主,2a,3a,3b及6a型各自占较大比例。早期HCV基因型较单一,随着时间推移,1b及2a亚型逐渐减少,而3a,3b及6a亚型逐年增加,亚型类型逐年增多。有偿献血人群lb,2a亚型所占比例较高;吸毒人群HCV基因亚型较多,3型(3a,3b亚型)及6a亚型所占比例较大,且有逐渐向普通人群扩散趋势。结论中国流行最广泛的HCV基因亚型为1b及2a,且分布地区差异较大,并随时间的推移,基因型分布产生较大变化。     

内蒙古部分地区乙肝病毒基因型分布特点研究

目的研究内蒙古部分地区HBV基因型的分布特点,为推测内蒙古地区乙肝的流行趋势提供数据资料。方法对内蒙古地区46份乙肝大三阳血样进行HBVDNA提取,之后用PCR法扩增HBV DNA的S基因片段,再对PCR体系进行基因测序,之后基因分型。结果B型1例(2.17%),C型43例(93.48%),D型2例(4.35%)。结论我区HBV DNA基因型分布以C型为主。     

人乳头瘤病毒基因型在宫颈癌及癌前病变中的分布

目的:了解丽水地区人乳头瘤病毒(HPV)基因型在宫颈癌及癌前病变中的分布。方法:采用HPV分型基因芯片检测系统对68例宫颈癌、62例宫颈上皮内瘤变患者进行HPV基因分型检测,以100例子宫颈炎患者的HPV基因型别作为参照。结果:子宫颈炎、宫颈上皮内瘤变和宫颈癌中HPV检出率分别为75.0%、84.0%和95.5%,其间差异比有显著性。在宫颈癌及癌前病变中,主要基因型分别为HPV16,58,53,52,68和18。结论:丽水市及周边地区宫颈癌及宫颈上皮内瘤变中HPV感染率很高,以16、58、53、52和68型最为常见。     

沈阳地区丙型肝炎患者HCV基因型分布调查

应用ＲＴ－ＰＣＲ型特异性引物方法对沈阳地区１００例抗ＨＣＶ及ＨＣＶＲＮＡ均阳性的丙型肝炎病人的血清标本进行ＨＣＶ基因分型。结果：ＨＣＶ－Ⅱ型感染占５８％，Ⅲ型占２７％，Ⅱ／Ⅲ混合型占１４％，未分型１％。提示沈阳地区ＨＣＶ感染以Ⅱ型为主，其次为Ⅲ型及Ⅱ／Ⅲ混合型，Ⅲ型及Ⅱ／Ⅲ混合型感染较其它地区高。     

Relationships of alcohol dehydrogenase 1B (<Emphasis Type="Italic">ADH1B</Emphasis>) and aldehyde dehydrogenase 2 (<Emphasis Type="Italic">ALDH2</Emphasis>) genotypes with alcohol sensitivity,drinking behavior and problem drinking in Japanese older men

Objectives

Many East Asians have the genetic polymorphisms rs1229984 in alcohol dehydrogenase 1B (ADH1B) and rs671 in aldehyde dehydrogenase 2 (ALDH2). Here we analyzed the relationships of the two genotypes with alcohol sensitivity, drinking behavior and problem drinking among older and younger men living in rural areas of Japan.

Methods

The subjects were 718 Japanese men aged 63.3 ± 10.8 (mean ± SD), categorized into the older (≥65 years, n = 357) and younger (<65 years, n = 361) groups. Facial flushing frequency, drinking behavior and positive CAGE results were compared among the genotypes using Bonferroni-corrected χ² test and a multivariate logistic regression analysis adjusting for age, BMI and lifestyle factors.

Results

The frequency of ‘always’ facial flushing among the ADH1B*1/*2 carriers was significantly lower than that among the ADH1B*2/*2 carriers in the older group (P < 0.01). The alcohol consumption (unit/day) in the ADH1B*1/*2 carriers tended to be higher compared with that in the ADH1B*2/*2 carriers among the older group (P = 0.050). In the younger group, no significant differences in alcohol sensitivity and drinking habits were generally found among the ADH1B genotypes. The ADH1B*1/*1 genotype tended to be positively associated with problem drinking in the older group (P = 0.080) but not in the younger group. The ALDH2 genotypes consistently and strongly affected the alcohol sensitivity, drinking behavior and problem drinking in both the younger and older group.

Conclusions

We for the first time observed a significant difference in alcohol sensitivity between ADH1B*1/*2 and ADH1B*2/*2 in older men aged 65 and above.

     

乙醛脱氢酶基因型对2-乙氧基乙醇代谢影响的研究

探讨乙醛脱氢酶（ALDH2）不同基因型代谢2－乙氧基乙醇（EE）的能力是否存在差异。方法 采用个体采样,毛细柱气相色谱分析技术及PCR检测方法,比较不同基因型个累计接触EE剂量与2－乙氧基乙酸（EAA）浓度对数值回归直线的回归系数。结果 ALDH2不同基因型个体累计接触EE剂量与EAA浓度对数值存在线性关系,A基因型回归系数大于B基因型。结论 ALDH2A基因型代谢EE能力强于B基因型。     

Population genetic and family studies on aldehyde dehydrogenase deficiency and alcohol sensitivity

Population genetic studies on the prevalence of aldehyde dehydrogenase isozyme I (ALDH I) deficiency in various Caucasian, Oriental, African, and American Indian subjects were carried out using hair roots as peripheral source of the enzyme activity. While a very high percentage of Orientals with Mongoloid origin were found deficient in ALDH I activity, no deficiency was detected in Caucasian and African populations. Native American Indians showed a relatively low incidence of ALDH I deficiency. A genetic model based on the phenotype determination using antisera against purified human liver ALDH I is proposed. Pedigree analysis of Japanese families suggests an autosomal codominant mode of inheritance.     

Aldehyde dehydrogenase and aldehyde reductase in isolated bovine brain microvessels

The activities of aldehyde dehydrogenase and aldehyde reductase were measured in microvessel fractions isolated from bovine brain. Aldehyde dehydrogenase specific activity in microvessels was enriched 1.5-fold over that measured in grey matter. The specific activity of aldehyde reductase was significantly lower in parenchymal vessles and microvessels than in grey matter. The presence of aldehyde dehydrogenase and aldehyde reductase in cerebral microvasculature is consistent with previous reports of enrichment of other enzymes involved in synthesis and degradation of monoamines. The enrichment of aldehyde dehydrogenase in cerebral microvasculature provides additional evidence for an enzymatic blood-brain barrier for biogenic aldehydes or ethanol-derived acetaldehyde.     

A two dimensional model of alcohol consumption: possible interaction of brain catalase and aldehyde dehydrogenase

The possible existence of a biological marker system mediating voluntary consumption of ethanol in rats has been examined in a series of studies. The working hypothesis underlying this research was that acetaldehyde, the primary metabolite of ethanol, mediates the positive reinforcing properties of ethanol and thus underlies the voluntary consumption of ethanol in both animals and humans. We further hypothesized that brain catalase and aldehyde dehydrogenase, the enzymes controlling the production and elimination of acetaldehyde in the brain, may represent a biological marker system underlying the affinity of the animals to consume ethanol. Data demonstrating that the activity levels of these enzymes are positively correlated with alcohol ingestion seems to suggest that it is likely that the enzyme activity can serve as a predictor of the propensity to drink alcohol. A predictive model is proposed which describes the modulation of voluntary ethanol intake through the activity of these enzymes and their role in determining rates of formation and degradation of acetaldehyde in the brain.     

Identification of aldehyde dehydrogenase resistant to cyanamide and disulfiram inhibition

A small number of Wistar rats from our breeding colony was identified whose mitochondrial low-K_m aldehyde dehydrogenase (ALDH) was resistant to inactivation by low (2.5 μM) concentrations of cyanamide, termed “resistant” by contrast to the typical animal labeled “sensitive.” Resistance could be due either to a lack of the hypothesized cyanamide-converting enzyme (catalase) or to the presence of different forms of ALDH. ALDH purified by affinity chromatography from either type of animal was not inhibited by cyanamide alone. Addition of intact “sensitive” mitochondria with cyanamide caused a great inhibition of purified cyanamide-sensitive ALDH but not of resistant ALDH. Similar results were obtained when catalase was used to convert cyanamide to its reactive derivative. Furthermore, disulfiram was observed to be less effective in inhibiting the cyanamide-resistant ALDH. These combined results are interpreted as indicating that resistance to cyanamide inhibition is due to a difference in ALDH isozymes and not to an artifact of the isolation process or to the absence of the cyanamide-activating enzyme.     

Human brain: aldehyde dehydrogenase activity and isozyme distribution in different areas

Three human post-mortem brains were dissected into seventeen areas and assayed for aldehyde dehydrogenase (EC 1.2.1.3) activity employing two assay systems: one at 68 microM and another at 13.6 mM propionaldehyde. The levels of activity with 68 microM propionaldehyde were significantly higher in cerebellum and putamen. The same brain areas were also examined by isoelectric focusing. By this procedure two distinct bands of aldehyde dehydrogenase activity (the cytoplasmic E1 and mitochondrial E2) could be readily visualized in cerebellum and putamen while other brain areas contained mainly the mitochondrial E2 isozyme.     

利用限制性片段长度多态性分析检测乙醛脱氢酶基因2的基因型

人类摄入酒精主要通过Ⅰ型酒精脱氢酶和乙醛脱氢酶共同催化。为建立乙醛脱氢酶基因２（ＡＬＤＨ２）的基因型检测方法，本研究应用限制性片段长度多态性分析法（ＲＦＬＰ－ＰＣＲ）测定ＡＬＤＨ２的基因型。根据ＡＬＤＨ２的基因序理资料，设计一含一个碱基替代的限制性内切酶ＭｂｏⅡ的可识别位点。随后ＤＮＡ模板在下列条件扩增；变性；９４，１ｍｉｎ，退火；５７℃，３ｍｉｎ，延伸；７２℃１ｍｉｎ。３５个循环。聚合酶链反应产     

Association of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 genotypes with fasting plasma glucose levels in Japanese male and female workers

AIMS: The objective was to clarify the effect of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) genotypes on the diabetic risk in Japanese workers. METHODS: At the time of mandatory health checkup, the ADH2 and ALDH2 genotypes, as well as fasting plasma glucose (FPG) levels, body mass index (BMI), smoking habit, and weekly alcohol intake, were examined in 492 men and 183 women working at motor vehicle dealerships. RESULTS: In using two-way analysis of variance to manipulate ADH2 and ALDH2 genotypes and alcohol intake (>70 g/week for men and >35 g/week for women), the FPG level after the adjustment for age, BMI, smoking habit, and another genotype was significantly higher in the men with ADH2*1/1 genotype than in those with the other genotypes, but there was no significant difference in the FPG level between the men with and without ALDH2*1/1 genotype. In contrast, the women with ALDH2*1/1 genotype had significantly lower FPG levels than those with the other genotypes, but there was no significant difference in the FPG level between the women with and without ADH2*1/1 genotype. Also, a significant interaction between ethanol intake and ALDH2 genotypes was seen only in the women. CONCLUSIONS: These findings suggest that genotypes of ADH2 and ALDH2 can modify the diabetic risk, irrespective of amounts of alcohol consumed. Also, there may be sex differences in the effect of these enzyme genotypes on glucose metabolism.     

Polymorphism of aldehyde dehydrogenase and ethanol elimination

The influence of polymorphism of aldehyde dehydrogenase (ALDH) on ethanol elimination was investigated. Japanese healthy male volunteers were divided into two groups, i.e., a normal ALDH group of 52 subjects with the low Km isozyme of ALDH, and a deficient group of 48 subjects without it. The subjects of the normal group were given 0.4, 0.8, 1.2, 1.6 or 2.0 g/kg of ethanol, while those in the deficient group ingested 0.4, 0.8 or 1.2 g/kg of ethanol. Widmark's factors (beta 60, Co and r) and ethanol elimination rate (ER) were compared between the two groups. In the deficient group, beta 60 and ER were not clearly elevated with the increase of ethanol dose, while those in the normal ALDH group increased depending on the blood ethanol level. Blood acetaldehyde level was elevated with the increase of the ethanol dose in the deficient group, but not in the normal group. In the experiment of the repeated ingestion of ethanol in the deficient group, the second peak of blood acetaldehyde level was lower than that of the first one.