华东汉族人群乙醇代谢酶相关SNP位点的多态性

目的对ADH2、ADH3、ALDH2和CYP2E1基因的40个SNP位点进行群体遗传学分析,得到多态性信息。方法利用PCR和质谱技术平台对SNP位点进行分型检测,通过对中国华东地区汉族人群199个无关个体的调查,统计分析40个SNP位点的等位基因分布频率。结果 40个SNP位点中,rs698、rs2241894（ADH3基因座）,rs13306164、rs671（ALDH2基因座）和rs28371746、rs2515641（CYP2E1基因座）的小等位基因分布频率（MAF）均大于1%,其它SNP位点的MAF均小于1%。结论 ADH2、ADH3、ALDH2和CYP2E1基因的40个SNP位点中,6个位点（rs698、rs2241894、rs13306164、rs671、rs28371746和rs2515641）在华东汉族人群中具有多态性。     

基因多态性、饮酒种类与乙醇代谢的相关性CSCD

目的探索ADH1B和ALDH2基因多态性以及饮酒种类对乙醇代谢的影响,为司法鉴定实践中涉及乙醇代谢结果解释或对血乙醇含量回推的案件提供数据支持。方法筛选出81名志愿者,通过多重SNa Pshot分型方法获得ADH1B、ADH1C和ALDH2的基因型。饮酒剂量为1.0 g/kg,在饮酒前以及饮酒后30 min、45 min、1 h、1.5 h、2 h、3 h、4 h、5 h、6 h、7 h和8 h静脉采血1 m L,通过顶空气相色谱法检测血中乙醇和乙醛的浓度,计算血乙醇达峰时间(T_(max))、乙醇峰值质量浓度(C_(max))、乙醇曲线下面积(area under curve,AUC_(乙醇))、AUC_(乙醛)和乙醇消除斜率(β)。为排除ADH1C基因多态性的干扰,选择携带ADH1C*1/*1基因型的个体,根据ADH1B和ALDH2的基因型分组,对各组上述参数进行单因素方差分析,并运用最小显著差异法进行组间比较,基因间的相互作用关系采用双因素方差分析。对3种饮酒种类(白酒、红酒和啤酒)组间的各参数进行随机区组设计方差分析。结果不同ADH1B和ALDH2基因型组间T_(max)和C_(max)差异无统计学意义,部分基因型组间AUC_(乙醇)、β和AUC_(乙醛)差异有统计学意义。个体饮相同剂量不同种类酒时,各组间各参数差异均无统计学意义。结论乙醇代谢受相关基因多态性影响较大,基本不受饮酒种类的影响。     

基因多态性、饮酒种类与乙醇代谢的相关性

目的探索ADH1B和ALDH2基因多态性以及饮酒种类对乙醇代谢的影响,为司法鉴定实践中涉及乙醇代谢结果解释或对血乙醇含量回推的案件提供数据支持。方法筛选出81名志愿者,通过多重SNa Pshot分型方法获得ADH1B、ADH1C和ALDH2的基因型。饮酒剂量为1.0 g/kg,在饮酒前以及饮酒后30 min、45 min、1 h、1.5 h、2 h、3 h、4 h、5 h、6 h、7 h和8 h静脉采血1 m L,通过顶空气相色谱法检测血中乙醇和乙醛的浓度,计算血乙醇达峰时间(T_(max))、乙醇峰值质量浓度(C_(max))、乙醇曲线下面积(area under curve,AUC_(乙醇))、AUC_(乙醛)和乙醇消除斜率(β)。为排除ADH1C基因多态性的干扰,选择携带ADH1C*1/*1基因型的个体,根据ADH1B和ALDH2的基因型分组,对各组上述参数进行单因素方差分析,并运用最小显著差异法进行组间比较,基因间的相互作用关系采用双因素方差分析。对3种饮酒种类(白酒、红酒和啤酒)组间的各参数进行随机区组设计方差分析。结果不同ADH1B和ALDH2基因型组间T_(max)和C_(max)差异无统计学意义,部分基因型组间AUC_(乙醇)、β和AUC_(乙醛)差异有统计学意义。个体饮相同剂量不同种类酒时,各组间各参数差异均无统计学意义。结论乙醇代谢受相关基因多态性影响较大,基本不受饮酒种类的影响。     

ALDH2基因多态性与乙醇代谢及外周乙醛积蓄程度的关系

目的了解不同乙醛脱氢酶2（acetaldehydedehydrogenase2,ALDH2）基因型人群饮酒后,其乙醇药代动力学和外周乙醛积蓄程度。方法收集无血缘关系的志愿者14名,采集静脉血液并且通过聚合酶链反应限制性片段长度多态性技术提取DNA并检测ALDH2基因型,按一定剂量饮酒后,以顶空气相色谱法于不同时间点同时测定血中乙醇及乙醛的含量并计算药代动力学参数。结果根据电泳结果,野生组为5名野生纯合型ALDH2＊1／＊1个体．突变组为9名突变杂合型ALDH2＊1／＊2个体,血中乙醇和乙醛分别在0～1570．7μg/mL和0～5．1772μg／mL范围内线性关系良好。突变组乙醇及乙醛药时曲线下面积（AUC）以及乙醇的末端消除半衰期（tl／2Z）均大于野生组,乙醇的经生物利用度校正的表观消除率（CL／F）小于野生组（P〈0．05）。结论饮酒后,ALDH2＊I／＊2突变组受酶活性抑制影响,血中乙醇和乙醛代谢减慢,造成外周乙醛的蓄积,从而进一步强化其在体内的作用。     

乙醇脱氢酶在酒精代谢中的作用

酒与人类社会生活密切相关,与酒相关的医学问题和法律问题已受到人们广泛关注。乙醇脱氢酶(ADH)为乙醇氧化分解的主要酶,本文就ADH的性质、ADH遗传多态性与乙醇代谢的关系、ADH不同家系在乙醇代谢中的作用以及ADH与乙醇代谢相关性疾病的关系进行综述,旨在为法庭科学和医学中的应用和研究提供参考。     

中国汉族和藏族CYP2E1基因RsaⅠ/PstⅠ基因座遗传多态性

CYP2E1(Cytochrome P450 2E1,CYP2E1)是二甲基亚硝胺D-脱甲基酶,它主要参与激活小分子致癌物如苯、四氯化碳和亚硝胺等,同时参与酒精的氧化代谢和产生自由基而启动脂质过氧化[1,2].本文调查了CYP2E1 RsaⅠ/PstⅠ基因座在中国汉族和藏族群体中的频率分布,为法医学实践提供必需的基础数据.     

血中乙醇及其代谢物乙醛、乙酸的顶空气相色谱法测定

本文用顶空气相色谱法,在 Porapak S 柱上测定人血中乙醇及其代谢物乙醛、乙酸。全血中乙酸在酸性条件下直接加入甲醇酯化成乙酸甲酯,改善了乙酸的挥发性和色谱行为。方法快速,简便,准确。应用本法测定两例正常人饮酒后血中乙醇、乙醛、乙酸浓度,结果表明血液乙醇浓度在酒后90分钟最高,而血液乙醛、乙酸浓度高峰则与人的乙醇代谢能力有关。     

中国汉族和藏族CYP2E1基因RsaI/PstI基因座遗传多态性

CYP2E1(Cytochrome P450 2E1,CYP2E1)是二甲基亚硝胺D-脱甲基酶,它主要参与激活小分子致癌物如苯、四氯化碳和亚硝胺等,同时参与酒精的氧化代谢和产生自由基而启动脂质过氧化[1,2]。本文调查了CYP2E1 RsaI/PstI基因座在中国汉族和藏族群体中的频率分布,为法医学实践提供必需的基础数据。1材料和方法1.1样品162名无血缘关系健康中国汉族个体和119名藏族个体血液样品为中国医科大学法医学院法医血清学教研室保存的样品。1.2方法DNA制备按常规酚-氯仿法[3]抽提,冷无水乙醇沉淀法提取基因组DNA。引物合成按参考文献[4]给出的序列合成…     

酒精在人体内的代谢动力学研究

将16名健康男性志愿者随机分为两组，分别按含酒精0．65g／kg和0．80g／kg体重的剂量给予酒精饮料，于酒后不同时间点采取静脉血样。用乙醇脱氨酶（ADH）氧化分析法测血样酒精浓度（BAC），所得浓度-时间数据经用药代动力学软件分析拟合。结果表明，酒精在人体内的代谢符合非线性消除伴一级吸收的一室开放模型。据此，作者建立了描述酒精在人体内动态变化规律的数学模型。经验证，该模型符合度良好，可用于司法实践。     

采血管中添加剂对血样中乙醇含量的影响

目的：探讨不同种类采血管对血样中乙醇含量检测结果的影响。方法分别用7种一次性真空采血管[无抗凝剂管、促凝剂管、分离胶-促凝剂管、枸橼酸钠（1∶4）管、枸橼酸钠（1∶9）管、柠檬酸钠（9∶1）管、EDTA-K2管]采集10名志愿者饮酒后2 h血液,用顶空气相色谱法检测血样中乙醇含量。结果相同血样用不同的采血管,其乙醇含量检测结果不同,依次为分离胶-促凝剂管〉促凝剂管〉无抗凝剂管〉EDTA-K2管〉枸橼酸钠（1∶9）管〉枸橼酸钠（1∶4）管,柠檬酸钠（9∶1）管与枸橼酸钠（1∶9）管检测结果基本一致。结论采集涉嫌酒后驾驶的驾驶员血样,应选用一次性真空采血管,首选EDTA-K2管。     

Genetically-induced variability of alcohol metabolism and its effect on drinking behavior and predisposition to alcoholism

Alcoholism is one of the most challenging current health problems in the Western countries with far-reaching medical, social, and economic consequences. There are a series of factors that interact in predisposing or protecting an individual against alcoholism and alcohol-related disorders. This article surveys the state of our knowledge concerning the biochemical and genetic variations in alcohol metabolism and their implications in alcohol sensitivity, alcohol drinking habits, and alcoholism in different racial/ethnic groups. The major pathway for the degradation of ethanol is its oxidation to hydrogen and acetaldehyde--to which many of the toxic effects of ethanol can be attributed. Variations in alcohol and acetaldehyde metabolism via genetically determined polymorphisms in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) seem to play an important role in individual and racial differences in acute and chronic reactions to alcohol, alcohol drinking habits, as well as vulnerability to organ damage after chronic alcohol abuse. Alcohol sensitivity and associated discomfort symptoms accompanying alcohol ingestion may be determinental for the significantly low incidence of alcoholism among the Japanese, Chinese and other Orientals of Mongoloid origin. An abnormal ALDH isozyme has been found to be widely prevalent among individuals of the Mongoloid race and is mainly responsible for the acute sensitivity to alcohol commonly observed in this race. Persons sensitive to alcohol by virtue of their genetically controlled ALDH isozyme deficiency may be discouraged from drinking large amounts of alcohol in their daily life due to the initial adverse reaction experienced after drinking alcohol. Indeed, a significantly low incidence of the mitochondrial ALDH isozyme deficiency has been observed in alcoholics as compared to psychiatric patients, drug dependents and healthy controls in Japan. How far any variation in ADH and/or ALDH activity among individuals of Caucasian origin will have similar effects has yet to be studied.     

Fatal acute alcohol intoxication in an ALDH2 heterozygote: a case report

On an evening in November, a 25-year-old man was found dead in his bedroom. There were many empty snap-out sheets for flunitrazepam tablets in the trash at his bedside. He had been beaten by a gang of young people earlier in the morning of the same day. At the medico-legal autopsy, although there were many bruises and/or abrasions on the whole body, only slight subdural hemorrhage was observed, and none of them was thought to be the cause of death. Flunitrazepam and its metabolites were not detected in his body fluid by gas chromatography-mass spectrometry (GC-MS). Marked lung edema and a severe congestion of organs were observed. His blood alcohol concentration from the femoral vein was 2.00 mg/ml. Fatal cases of acute alcohol intoxication usually have shown higher alcohol concentration (2.25-6.23 mg/ml). Although the genotype of aldehyde dehydrogenase 2 (ALDH2) has not previously been mentioned as a contributing factor in determining the cause of death, in this case the genotype of ALDH2 was ALDH2*1/2 and thus is important. Those who possess the ALDH2*2 gene show high concentrations of acetaldehyde (AcH) at even comparatively lower alcohol levels. Consequently, the cause of death was considered to be acute alcohol intoxication including AcH poisoning.     

Experimental studies on the mechanism of ethanol formation in corpses

Various in vitro experiments were performed for the purpose of clarifying the mechanism of ethanol production in corpses. Whereas a negligible quantity of ethanol was produced in the blood alone, which was left at room temperature, the quantity of ethanol was slightly increased by addition of glucose to the blood. When saprogens were further added, the quantity was markedly increased. Various materials were added to blood-liver homogenates as specimens, and the mixtures were stored in an incubator at 37 degrees C. As a result of the addition of an antibiotic to the mixture every day, there was hardly any production of ethanol. When alcohol dehydrogenase (ADH) and reduced nicotinamide adenine dinucleotide (NADH) were added, ethanol production was slightly increased. When acetaldehyde was added first, ethanol production was inhibited the next day, but on and after day 2, the quantity of ethanol was more than that in the control material. When pyruvic acid was added first, the results were similar to the above. Pyrazole, cyanamide, and disulfiram completely inhibited the production of ethanol. Ethanol production in corpses is believed to take place through a pathway opposite to that of ethanol metabolism in the living body, under the influence of ADH, ALDH, etc., in saprogens using carbohydrates as substrates.     

Determination of the effects of alcohol dehydrogenase (ADH) 1B and ADH1C polymorphisms on alcohol dependence in Turkey

Alcoholism is a complex genetically influenced disorder which refers to alcohol abuse and alcohol dependence. There are controversial results on the role of gene polymorphisms in alcohol dependence in the literature. Differences in population groups and selective inclusion criteria for alcohol dependence may affect results. In this study, we investigated the role of ADH1B Arg48His (rs1229984) and, ADH1C Ile350Val (rs698) gene polymorphisms in Turkish population. 100 healthy volunteers and 75 patients who were admitted to Ege University Alcohol Dependence Unit enrolled in the study. We found significant increase both in ADH1B (Arg48His) polymorphism Arg allele and Arg/Arg genotype frequency in patients. No profound connection between alcohol dependence and ADH1C Ile350Val gene polymorphism was detected. Alcohol dependence is an important health problem that depends on many genetic and environmental factors but we think that it is possible to interpret genetic risk for developing early diagnostic methods and treatment strategies by comprehensive linkage and association studies.     

Forensic medical significance of enzymatic products of ethanol oxidation in cadaveric brain

The concentrations of ethanol, acetaldehyde, and the oxidizing enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (AIDH) were measured in neuronal cytoplasm, limbic cortical capillaries, and cardiovascular center of the medulla oblongata. The measurements were carried out by histochemical methods, gas-liquid chromatography, etc. The results were processed with consideration for the degree and stage of ethanol intoxication in case of death from ethanol poisoning and asphyxia in hanging. Increase of ethanol concentration in the blood was associated with a decrease and then increase in the brain concentrations of ADH and with an increase of AIDH concentration. Enzymatic changes predominated in capillary walls; the minimum shifts were observed in the neuronal cytoplasm of the cerebral limbic cortex, which confirms the neurohumoral nature of detoxication regulation. Lethal ethanol poisoning could occur during any stage of ethanol intoxication. The detected changes in ethanol, acetaldehyde, and metabolizing oxidoreductases in brain tissue can be used for forensic medical diagnosis of ethanol poisoning.     

Histochemical changes in the hypothalamus, hypophysis, and adrenal glands observed in ethanol poisoning

A comprehensive morphological-and-histochemical study of neuroendocrinal internals in cases of ethanol poisonings was undertaken. Actual forensic medical materials were used (62 cadavers) to make morphometry examinations of the hypothesis and adrenal glands. Besides, the distribution of alcohol dehydrogenase and acetaldehyde dehydrogenase was investigated in the mediatory differential brain sections, i.e. cerebellum, locus coeruleus, dorsal raphe nucleus, hypothalamus and adrenal glands. A differential distribution of ethanol-oxidizing enzymes as well as their changes in ethanol lethal poisoning were established; additionally, a variety of morphological signs were defined, which enable the differential diagnosis of a death reason in acute alcoholic intoxication.