乙醇、乙醛慢代谢与酒后驾车肇事

在体内乙醇代谢过程中起重要作用的酶有乙醇脱氢酶（ADH）、乙醛脱氢酶（ALDH）和细胞色素P4502E1酶（CYP2E1）,它们均具有基因多态性,不同基因型个体对乙醇的耐受性存在差别,表现为酒后的行为反应能力不同。司机若为慢代谢型,乙醇、乙醛代谢速率低下,即使少量饮酒,酒后开车也可造成交通肇事。通过对ADH、ALDH和CYP2E1基因多态性与乙醇、乙醛代谢能力的关系进行综述。     

云南汉族NR3C1基因多态性与暴力攻击行为相关性

目的为了探讨云南汉族人群糖皮质激素受体基因(NR3C1)多态性与攻击行为的相关性。方法应用改良多重高温连接酶反应(improve multiplex ligasedetection reaction,iMLDR)技术检测194例云南汉族有攻击行为的监狱服刑人员和301例健康对照样本的NR3C1基因SNPs(rs6190、rs6191、rs6198、rs41423247、rs56149945)基因型,采用SPSS19.0软件、PHASE2.1平台进行统计学分析。结果 rs6191和rs41423247单个基因座的等位基因分布在非攻击组与攻击组、抢劫亚组和故意伤害亚组中均无显著性差异;rs41423247的基因型在非攻击组与抢劫亚组中的分布有显著性差异(p=0.048);构建的4种单倍型分布在非攻击组与攻击组、抢劫亚组和故意伤害亚组中均无显著性差异。结论云南汉族人群NR3C1基因的rs41423247基因座的单基因座多态性可能与指向他人的躯体攻击行为相关,rs6191基因座的单基因座多态性可能与暴力攻击行为无关。     

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。     

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.     

COMT基因与精神分裂症患者暴力攻击行为关联性的研究进展

精神分裂症患者的暴力攻击行为发生率高于一般人群,暴力攻击行为在某些方面具有显著的遗传倾向性,与精神分裂症患者暴力攻击行为研究最多的是儿茶酚氧位甲基转移酶（catechol-O-methyltrans-ferase , COMT ）基因。本文从COMT Val158Met 和COMT Ala72Ser 的SNP 多态性、COMT 基因单倍型、COMT基因启动子区DNA甲基化等方面对COMT基因变异与精神分裂症患者暴力攻击行为的相关性研究进行综述,并提出精神分裂症患者暴力攻击行为的遗传学研究方向。     

GABA Receptors,Alcohol Dependence and Criminal Behavior

The aim of this study was to analyze the connection between alcohol dependence and criminal behavior by an integrated genetic–environmental approach. The research, structured as a case–control study, examined 186 alcohol‐dependent males; group 1 (N = 47 convicted subjects) was compared with group 2 (N = 139 no previous criminal records). Genetic results were innovative, highlighting differences in genotype distribution (p = 0.0067) in group 1 for single‐nucleotide polymorphism rs 3780428, located in the intronic region of subunit 2 of the GABA B receptor gene (GABBR2). Some environmental factors (e.g., grade repetition) were associated with criminal behavior; others (e.g., attendance at Alcoholics Anonymous) were inversely related to convictions. The concomitant presence of the genetic and environmental factors found to be associated with the condition of alcohol‐dependent inmate showed a 4‐fold increase in the risk of antisocial behavior. The results need to be replicated on a larger population to develop new preventive and therapeutic proposals.     

Mutational analysis of TTN,TCAP and TPM1 in cardiomyopathy

Resent molecular genetic study revealed that defects in sarcomeric genes causes cardiomyopathies. Comprehensive screening of 3 sarcomeric genes: TTN (titin), TCAP (telethonin) and TPM1 (alpha-tropomyosin) were performed in 35 consented autopsy cases diagnosed as cardiomyopathy. One nonsynonymous mutation p.Val9710Ile detected in TTN, which located on binding region to cardiac ankyrin repeat protein was found in one DCM case. It was suggested that the mutation might alter interaction of the Z-disc components and caused cardiomyopathy. A single nucleotide polymorphism p.Ala151= found in TCAP had significant differences in gene frequency between DCM and control cases. It is necessary to analyze the other sarcomeric genes and clarify the relationship with aetiology.     

Analysis of Dopamine D2 Receptor (DRD2) Gene Polymorphisms in Cannabinoid Addicts*

Abstract: The gene encoding the dopamine D2 receptor (DRD2) has been suggested as a candidate gene for substance dependence. In this study, the possible association between Taq1A and Taq1B DRD2 polymorphisms and cannabinoid dependence was investigated. One hundred and twelve cannabinoid addicted and 130 healthy control subjects were included in this study. The Taq1A and Taq1B genotypes were determined in all subjects by polymerase chain reaction. For each polymorphism (A or B), the subjects were categorized into three groups according to their genotype, that is, the subjects with alleles A1/A1, A1/A2, A2/A2; B1/B1, B1/B2, and B2/B2. A significant association was found between Taq1A gene polymorphism and cannabinoid addicts compared to the control subjects. This finding suggests that polymorphism of the Taq1A, but not the Taq1B, may be associated with the susceptibility to cannabinoid dependence. Further clinical studies are required to be carried out for confirmation and evaluation of these findings.     

偏执型精神分裂症患者GRIN1基因-855G/C与-1140G/A位点的遗传多态性

目的探讨GRIN1基因启动子区两个单核苷酸多态性位点-855 G/C、-1140 G/A遗传多态性与偏执型精神分裂症的相关性及法医学意义。方法采用PCR限制性片段长度多态性(restriction fragment length polymorphism,RFLP)结合PAGE法对中国北方汉族183例健康无关个体和172例偏执型精神分裂症患者GRIN1基因5′端的-855 G/C和-1140 G/A位点多态性进行检测,采用χ2检验人群中基因型分布是否符合Hardy-Weinberg平衡定律,并比较两组人群中基因型和等位基因频率分布的差异。结果两组群体基因型分布符合Hardy-Weinberg平衡定律。-855 G/C位点基因型分布在对照组女性和实验组女性间的差异具有统计学意义(P0.05),-1140 G/A位点基因型和等位基因频率分布在对照组和实验组间及两组女性间差异具有统计学意义(P0.05)。结论 GRIN1基因启动子区-1140 G/A位点单核苷酸多态性可能与精神分裂症存在相关性;精神分裂症发生的遗传学因素可能存在性别倾向,可为精神分裂症的司法鉴定提供参考。     

Molecular Autopsy of Desmosomal Protein Plakophilin‐2 in Sudden Unexplained Nocturnal Death Syndrome

Plakophilin‐2 (PKP2) variants could produce a phenotype of Brugada syndrome (BrS), which seems to be most likely the same allelic disorder as some sudden unexplained nocturnal death syndrome (SUNDS). All coding regions of PKP2 gene in 119 SUNDS victims were genetically screened using PCR and direct Sanger sequencing methods. Three novel mutations (p.Ala159Thr, p.Val200Val, and p.Gly265Glu), one novel rare polymorphism (p.Thr723Thr), and eight reported polymorphisms were identified. A compound mutation (p.Ala159Thr and p.Gly265Glu) and a rare polymorphism (p.Thr723Thr) were found in one SUNDS case with absence of the cardiomyopathic features. The detected compound mutation identified in this first investigation of PKP2 genetic phenotype in SUNDS is regarded as the plausible genetic cause of this SUNDS case. The rare incidence of PKP2 mutation in SUNDS (1%) supports the previous viewpoint that SUNDS is most likely an allelic disorder as BrS.     

谷氨酸受体基因单核苷酸多态性与精神分裂症的关联

谷氨酸是人类神经系统中重要的兴奋性神经递质,通过与受体结合发挥生物学作用.当编码受体的基因异常时,可能导致精神疾病发生.本文通过回顾相关研究,发现诸如GRIN1、GRIN2B、GRM3等受体基因上的rs11146020、366C/G、rs1468412与精神分裂症相关联;同时也存在矛盾的研究结果,表明精神分裂症可能为多因素、多位点、多基因复杂遗传疾病.部分位点如GRIN2B上的366C/G、2664C/T,GRIK2上的rs1408766(C/T)的遗传多态性较好,可能成为法医学个人识别与亲权鉴定的新指标.该领域研究在司法精神病的鉴定工作中可能具有潜在的意义.     

云南汉族CRHBP基因多态性与暴力攻击行为的相关性

目的探讨云南汉族人群促肾上腺皮质激素释放激素结合蛋白(corticotropin releasing hormone-binding protein, CRHBP)基因多态性与暴力攻击行为的相关性。方法对云南汉族111例有攻击行为的服刑人员(包含53例抢劫,58例故意伤害)和189例健康对照样本采用改良的多重高温连接酶检测反应技术(improve Multiplex ligase detection reaction, iMLDR)检测CRHBP基因的4个Tag SNPs(rs10062367, rs32897, rs7718461, rs7721799)的基因型,应用SPSS 20.0和SHEsis软件对结果进行统计分析。结果 rs32897、rs7718461、rs7721799的等位基因和基因型分布在暴力组、抢劫亚组、故意伤害亚组和对照组中均无显著差异(P>0.05),rs10062367等位基因和基因型分布在暴力组、抢劫亚组和对照组中也无显著差异(P>0.05),但在故意伤害亚组与对照组中具有显著差异(P<0.05)。单倍型ATGA可使暴力的相对风险显著增高(P<0.05),单倍型GCAA可使指向他人暴力的相对风险显著增高(P<0.05)。结论 CRHBP基因rs10062367位点多态性可能与云南汉族人群针对他人的攻击行为有关,单倍型ATGA是暴力行为的风险因子,个体携带单倍型GCAA会使指向他人的躯体攻击行为风险增加。     

广东汉族人群H19基因上游差异甲基化区SNP

目的调查广东汉族人群中H19基因上游差异甲基化区(differentially methylated region,DMR)的单核苷酸多态性(SNP)及单倍型。方法应用PIA分型法,以限制性内切酶Mcr BC、HpaⅡ消化基因组DNA分别获得个体单亲源DNA模板链,经测序,分别获得个体H19基因上游DMR单亲源SNP等位基因、基因型及单倍型数据。结果共检出13个SNP(rs10840167、rs2525883、rs12417375、rs4930101、rs2525882、rs2735970、rs2735971、rs11042170、rs2735972、rs10732516、rs2071094、rs2107425、rs4930098)及1个突变点(g7351c)。所有位点经统计学分析均符合Hardy-Weinberg平衡定律(P0.05)。除rs12417375位点DP值为0.279,其余12个SNP DP值在0.446~0.614;g7351c突变点DP值为0.013,提示为南方汉族民族特异性位点。共检出8种单倍型(命名为单倍型1~8),其中有3种为新发现的单倍型,其DP、PIC、PE及H分别为0.891、0.714、0.524和0.758。结论 PIA分型法获得的H19基因上游DMR SNP位点及其单倍型遗传标记系统具有较高的鉴别能力,在法医学鉴定中具有较好的实用价值。     

Analysis of 50 SNPs in CYP2D6, CYP2C19, CYP2C9, CYP3A4 and CYP1A2 by MALDI-TOF mass spectrometry in Chinese Han population

One of the major challenges in the near future is the identification of genes that affect the metabolism of different drugs. Large scale association studies that utilise single nucleotide polymorphisms (SNPs) have been considered a valuable tool for this purpose. CYP2D6, CYP2C19, CYP2C9, CYP3A4 and CYP1A2 were found to be involved in the majority of hepatically cleared drugs. To determine the allele frequencies of some SNPs that may have great potential value in forensic science, we screened 50 SNPs in these 5 CYP genes in Chinese Han people using an accurate, high-throughput, cost-effective method. Primers were designed using the MassARRAY Assay Design software. Genomic DNA was prepared from blood samples obtained from individuals of Chinese Han origin. Multiplex PCR was performed to amplify the relevant gene fragments, and the polymorphisms were analysed by allele-specific primer extension followed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). A panel of genomic DNA samples previously genotyped by other methods were analysed simultaneously for quality control, and the results demonstrated that this assay was 100% accurate. A total of 17 of the analysed SNPs were polymorphic. Of these 17 SNPs, 8 (rs16947, rs28371725, rs1800754, rs4244285, rs4986893, rs12248560, rs3758580, rs2242480) had an allele frequency that was significantly different between this Chinese Han population and Caucasians (p<0.01). In addition, the frequencies of two of these SNPs (rs1800754, rs3758581) in our Chinese Han population differed significantly from the existing Chinese frequency data (p<0.01). The described method thus provides reliable results and enables the genotyping of up to thousands of samples by taking advantage of the high-throughput MALDI-TOF technology. The results herein are now included as a supplement to the P450 database.     

Determination of phenotype associated SNPs in the MC1R gene

Prediction of physical appearance based on genetic analysis is a very attractive prospect for forensic investigations. Recent studies have proved that there is a significant association between some genetic variants of the melanocortin 1 receptor (MC1R) gene and red hair color. The present study focuses on the potential forensic applicability of variation within this pigment-related gene. Sequencing of the complete MC1R gene was performed on a group of red-haired individuals and controls with different pigmentation. A major role in determination of red hair color is played by two MC1R variants--C451T and C478T. The optimized minisequencing assay for genotyping of the above positions and three other important red hair-related MC1R polymorphisms, C252A, G425A, and G880C was successfully applied to analyze typical forensic specimens. Determination of a homozygous or heterozygous combination can be a good predictor of both red hair color and fair skin of a subject.     

单核苷酸多态性研究进展

单核甘酸多态性（ SNPs）是继 RFLP和微卫星多态性标记之后的新一代遗传标记系统,具有密度高、遗传稳定、分析易自动化等特点。 SNPs可通过电泳、 PCR、酶切及测序等方法检测,已广泛应用于基因作图、疾病相关性分析、群体遗传学及药物研究等领域。     

Y染色体3个SNP基因座及其单倍型的遗传多态性和群体差异

目的 探讨人类Y染色体3个SNP基因座及其单倍型的遗传多态性和群体差异。方法 应用PCR-RFLPs结合DNA序列分析技术,对140例来自中国藏族、日本、南非黑人及南非白人男性的Y染色体M4、M9和M122基因座的等位基因进行分析。结果 全部样品M4基因座的等位基因均为野生型M4A,未发现多态性。共检出3种单倍型,黑人个体均为野生型单倍型M4A/M9C/M122T。白人个体有8例单倍型为M4A/M9G/M122T,未检出等位基因M122C。日本及中国藏族群体以单倍型M4A/M9C/M122T为主,频率分别为0.50和0.65,未检出单倍型M4A/M9C/M122C,个人识别机率与父权排除率分别为0.6191和0.4994。单倍型频率分布在中国藏族和日本群体之间存在显著性差异(P<0.01)。结论 单倍型M4A/M9G/M122C为亚洲人特征,M9和M122基因座在中国藏族和日本群体中具有较高的遗传多态性,并显示出明显的人种和群体差异。     

DNA polymorphisms in the tyrosine hydroxylase and GNB3 genes: association with unexpected death from acute myocardial infarction and increased heart weight

Sudden and unexpected death from myocardial infarction (MI) is one of the most commonly observed findings in forensic medicine. To investigate the biochemical and genetic background of this disease we investigated the genotypes for two polymorphisms associated with hypertension: TH01, a tetrameric microsatellite in the tyrosine hydroxylase gene and the single nucleotide polymorphism C825T in the GNB3 gene in 116 sudden deaths from MI (78 males, 38 females) and in a control group of 137 deaths from natural causes other than MI (52 males, 85 females). For TH01 no correlation with the prevalence of MI was found. For C825T, results were different. While for the male individuals allelic frequencies and genotype distributions were similar in both groups, T-homozygosity was significantly more common in female fatalities from MI than in the female control group (24% versus 7%; Relative Risk 2.29). Nevertheless, neither for TH01 nor for C825T an association with heart weight was found. Thus our results demonstrate that the C825T polymorphism may play a role in the development of myocardial infarctions, at least in females. They also demonstrate that the genetic component in complex diseases like MI may depend on the gender of the patients. As the influence of this polymorphism on arterial blood pressure appears to be relatively small, and G-proteins are involved in numerous intracellular signal cascades it can be speculated that T-homozygosity at this locus might influence the incidence or mortality of cardiovascular disease via hitherto unknown mechanisms.     

DGGE技术检测小核核糖核蛋白多肽N基因rs220030位点的多态性

目的 分析小核核糖核蛋白多肽N(small nuclear ribonucleoprotein polypeptide N,SNRPN)基因SNP位点rs220030在中国汉族人群中的基因结构特征及多态性,获得群体遗传学资料.方法 应用变性梯度凝胶电泳(denatu^ng gradient gel electropho...     

Prevalence of alcohol in blood samples from traffic accident cases in Turkey

Alcohol is one of the main causes of traffic accidents worldwide. With a population of 70 million, 12 million vehicles, and 18 million drivers (16% women), Turkey is one of the European countries that has a high incidence of road traffic accidents.In accordance with Turkish laws, subjects were considered to be positive when alcohol blood concentration exceeded 50 mg/100 mL. The objective of the present study was to obtain reliable and comparable data about alcohol use in traffic cases in Turkey. All cases are admitted to the emergency department at Ege University Medical Faculty. The cases from police officers are described as traffic control cases. Alcohol was detected in the blood of about 54.4% of the traffic-related cases during October 2005 to March 2007. It has been observed that, in 17.4% of the traffic accident cases, the blood alcohol level was 50 mg/dL or less, which is the legal limit in Turkey for car drivers. Alcohol prevalence was 57.2% in male cases and 43.6% in female cases. In alcohol-positive cases; the ratios for males were 1.73 times more frequent in traffic-related cases. Prevalence data will help traffic safety professionals to adequately allocate resources and plan future efforts in reducing drinking-and-driving behavior and thereby reduce traffic accidents.