复杂疾病病因研究中基因问交互作用分析:基于基因型传递不平衡的多因子降维法

介绍复杂疾病病因研究中分析基因-基因交互作用的一种新方法：基于基因型传递不平衡的多因子降维法（MDR-PDT）。文中简述MDR-PDT的基本原理、步骤及特点，并结合研究实例说明其应用过程。MDR-PDT是原始MDR的扩展，可用于多种结构类型的核心家系资料分析基因-基因交互作用。结论MDR-PDT具有非参数、无需遗传模式的特点，并能充分利用家系中多个家庭成员的信息，在复杂疾病病因研究中分析基因-基因交互作用具有良好的效能。     

病例对照方法在基因环境交互作用研究中的应用

现代流行病学研究越来越重视基因与环境交互作用，要研究基因环境交互作用，需要有基因型、表现型（患病与否）与环境暴露信息，由于基因型测定需要有尖端技术、设备，而且耗资巨大，不是首选方法，人们往往首先采用替代性方法对研究对象进行基因型分类。病例对照研究是流...     

代谢酶基因多态性与环境暴露交互作用的分析方法及其应用

目的 以肿瘤易感基因谷胱苷肽-S转硫酶（GST）M1缺失基因型为例,说明基因与环境暴露交互作用的分析方法以及应用。方法 采用社区为基础的病例对照研究方法,代谢酶基因多态性的检测用PCR技术,资料分析用多因素logistic回归模型。研究对象为1997年1月至1998年12月经扬中市人民医院确诊,肠型胃癌病例112例,以同期该地无上消化道肿瘤“健康”人群为对照,共675例。结果 调整混杂因素后,GST M1缺失基因型与既往吸烟史的交互作用系数为3.38,OReg值达8.40,有极显著意义,为4型交互作用中的超相乘模型;GST M1缺失基因型与吸烟量的交互作用呈高暴露-基因效应,交互作用系数分别为0.995、2.085和2.157,即随着暴露剂量增加,交互作用强度也逐渐增加;与饮酒量呈低暴露-基因效应,交互作用系数分别为1.01和0.97,交互作用强度随暴露剂量增加而逐渐降低。结论 基于logistic模型的分析方法,可用于评价基因-环境之间的交互作用,以及剂量反应关系的暴露基因效应。     

应用多因子降维法分析基因-基因交互作用

目的介绍在遗传流行病学病例对照研究中,应用多因子降维法（MDR）分析基因-基因交互作用.方法简述MDR的基本步骤、原理及其特点,并结合研究实例说明在病例对照研究中如何应用软件进行MDR分析.结果相对于传统的统计学方法,MDR是一种无参数、无遗传模式的分析交互作用的方法,理论和实例研究均表明其分析交互作用具有较好的效能,目前已成功应用于散发性乳腺癌、心房颤动和原发性高血压等疾病的研究.结论 MDR能够应用于病例对照研究进行基因-基因交互作用的分析,且具有较传统的统计学分析方法无法比拟的优势.     

细胞色素P4501A1基因多态性在胃癌发生中的交互作用

目的：探讨CYP1A1突变基因型与吸烟、饮酒因素对胃癌发生的交互作用及作用方式。方法：以社区为基础的病例对照研究,病例为胃镜及病理确诊的肠型胃癌,共112例,以同期上消化道肿瘤病例的“健康”同胞、配偶和配偶的同胞为对照组,共676例,用多聚酶链反应和限制性片段长度多态性法检测其基因型,多基因logistic回归模型分析与胃癌的相关性。结果：在调整混杂因素的影响后,未见CYP1A1突变基因型与胃癌危险性之间有统计学关联;但CYP1A1基因型与吸烟对胃癌发生有明显交互作用,显增加胃癌的危险性,交互作用系数γ为2．82,OReg值为5．00,为2型交互作用中的超相乘模型,进一步分析剂量反应关系显示;突变基因型与吸烟量,开始吸烟年龄均呈“低暴露－基因效应”方式。即随着暴露剂量的增加,交互作用的强度逐渐降低。CYP1A1突变基因型与饮酒史的交互作用有减弱效应,OReg值为2．22,γ为0．46,但呈“高暴露－基因效应”。结论CYP1A1突变基因型与吸烟、饮酒对胃癌均有交互作用,但交互作用的方式不同。这些结果提示CYP1A1突变基因型的个体应完成戒烟、限制大量饮酒、以预防胃癌的发生。     

基因多态性在肺癌发生中交互作用

目的探讨代谢酶基因与修复酶基因多态性在肺癌发生中的交互作用。方法采用1：1配对病例一对照研究，收集原发性肺癌患者227例和相应非肿瘤对照227例，对CYP1B1、CYP2C19、CYP2D6、CYP2E1、GSTM1、GSTT1、GSTP1、mEH、NQ01、XRCC1、XRCC3、hOGG1、NAT2、XPD基因多态性进行检测，应用Logistic回归对基因一基因交互作用进行分析。结果CYP2C19突变基因型与NQ01突变基因型。mEH-exon3突变基因型与NQ01突变基因型之间对肺癌的发生存在交互作用，可导致肺癌易感性的增高。未见其他代谢酶基因与修复酶基因在汉族人群肺癌发生中存在交互作用。结论对基因多态性的联合检测更有利于筛选易感人群。今后应加大样本含量，进行多基因之间的联合作用分析。     

用叉生分析探讨SLC2A9基因与BMI的交互作用对高尿酸血症的影响

目的 探讨SLC2A9基因的rs1014290位点和rs7442295位点与体质指数（body mass index，BMI）之间的交互作用对高尿酸血症的影响，为研究高尿酸血症的病因提供理论依据。方法 采用宁夏某体检机构定期进行体检已确定的366例高尿酸血症患者为病例组，按照性别、民族、年龄采用1:1配对的方法选取同时期、同体检机构进行体检的366例健康人作为对照组。用叉生分析研究基因位点与BMI之间的交互作用。结果 病例组的肌酐（creatinine，Crea）、总胆固醇（total Cholesterol，TC）、甘油三酯（triglyceride，TG）、BMI比对照组高，差异均有统计学意义（均有P<0.05）。rs1014290位点的基因型在病例组与对照组之间差异有统计学意义（χ2=13.117，P=0.004）。rs1014290位点的不同遗传模型基因型构成在病例组与对照组之间差异有统计学意义（χ2=11.225，P=0.001），携带GG基因型发生高尿酸血症的可能性是携带GA+AA基因型发生高尿酸血症的47.4%。rs1014290位点与BMI的叉生分析中，基于相加模型有统计学意义（U=4.874，P=0.032），S=-2.022，AP=0.674，AP*=1.495，RERI=1.227，基于相乘模型有统计学意义（P=0.017），ORint=4.123。结论 rs1014290位点与BMI之间存在相加和相乘的交互作用。     

2型糖尿病与脂联素基因及行为因素相互关系的研究

目的研究2型糖尿病与脂联素基因及行为因素的相互关系。方法对上海市浦东新区常住居民中新发糖尿病病人（糖尿病组）及社区正常人群（对照组）各590人进行病例一对照研究，利用单因素和多因素非条件Logistic回归分析。结果脂联素SNP＋276三种基因型和等位基因分布差异有统计学意义，糖尿病组中G／G基因型多于对照人群。通过单因素分析显示，SNP＋276、职业体力活动、每周锻炼时间、饮酒与糖尿病关系有统计学意义。通过多因素分析显示，职业体力活动、休闲体力活动、每周锻炼时间、饮酒等指标均有统计学意义，其中休闲时体力活动是2型糖尿病的保护因素，同时脂联素SNP＋276与每周锻炼时间交互作用有统计学意义，较长锻炼时间能使糖尿病患病风险降低。结论脂联素基因、行为因素均与2型糖尿病有关，同时二者存在交互作用。     

基因-环境交互作用

基因-环境交互作用(gene—environment interaction)一般可以从统计学交互作用和生物学交互作用两个角度来理解。统计学基因一环境交互作用指的是对于含有不同基因型的个体，环境因素与健康效应间的统计学关联的程度或方向不同，或者对于处于不同环境暴露条件下的个体，基因型与健康效应间的统计学关联的程度或方向不同。生物学基因一环境交互作用指的是基因和环境因素彼此依赖的影响一个生物学表型，缺少其中任何一个因素，疾病均不会发生，一般不要求必须具有统计学交互作用。     

血脂与ACE基因多态性对糖尿病肾病交互作用

目的探讨血管紧张素Ⅰ转换酶（ACE）基因的插入／缺失多态性与高血脂因素对糖尿病肾病发生的交互作用及其强度。方法采用聚合酶链反应技术检测109例2型糖尿病（T2MD）患者（其中合并肾病患者37例。未发生肾病患者72例）ACE基因插入／缺失多态性，用相加模型分析其与高血脂对糖尿病合并肾病的交互作用。结果糖尿病肾病患者的DD基因型频率高于无肾病糖尿病患者组（75．7％和55．6％，P=0．040），D等位基因频率也有升高的趋势，差异接近显著性水准（87．8％和77．1％，P=0．057）。肾病组甘油三酯水平高于单纯糖尿病组，差异有统计学意义（P=0．049）。ACE基因DD基因型与血脂对糖尿病肾病发生有明显正交互作用，与总胆固醇、甘油三酯的交互作用系数分别为2．17，4．29，归因交互百分比分别为42．03％，62．60％，OR（AB）值分别为4．52和10．75。结论ACE基因的DD基因型可能增高2型糖尿病患者并发肾病的易感性，并且与高总胆固醇、高甘油三酯有交互作用。     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.