冠心病猝死的遗传学研究进展

冠心病是威胁人类健康的重要疾病,猝死作为冠心病最严重的类型,具有发病突然、救治成功率低等特点。目前无有效手段对冠心病猝死实施精准预测。随着遗传学研究的不断深入,冠心病猝死的遗传背景 被不断揭示,越来越多的遗传位点被证实与冠心病猝死相关,使得猝死的早期识别成为可能。本文从冠心病猝死的基因多态性、相关RNA和表观遗传学三方面,对冠心病猝死的遗传学研究进展做一综述,旨在从微观层面加强对冠心病猝死的认识。     

蒙古族ACE、AGT M235T基因多态性与环境因素对高血压的交互作用

原发性高血压（essential hypertension, EH）是常见的心血管病,也是其他心血管病的重要危险因素,是全球性的公共卫生问题.目前认为,高血压是多种遗传因素和环境因素共同作用而引起的复杂性状疾病,在人类遗传易感性的基础上,在环境危险因素的作用下发病.     

全基因组关联研究在冠心病遗传学中的应用进展

冠心病的遗传因素研究是发病机制研究的重要组成部分,全基因组关联研究策略的发展使得其在探究冠心病的遗传因素及发病机制上具有巨大的价值,随着流行病学的进一步发展及应用,将遗传学和流行病学的研究设计方法相结合,已成为目前全基因组关联研究策略的重要方法。在此对近年国内外该方面的研究进展进行归纳总结,探讨存在的问题,并对未来发展趋势作一展望。     

家族孤立性阵发心房纤颤2例并家系调查

心房纤颤（房颤）是最常见的心律失常之一。房颤是一种多因素疾病,年龄、高血压性心脏病、心肌病、瓣膜疾病和冠心病等是房颤发生的高危因素。近年来研究发现分子遗传因素在该病的发生发展中具有重要作用。本文通过对二例孤立性房颤的病例特点分析及家系调查,发现其家族四代56人中共有8例经冠状动脉造影或CT显影证实为孤立性房颤患者,初步验证了房颤的遗传学因素,为今后房颤的分子生物学和遗传学研究奠定了事实基础。     

冠心病与载脂蛋白AI／CⅢ,B基因多态性

冠心病与载脂蛋白ＡＩ／ＣⅢ、Ｂ基因多态性李玉宏刘仁光（心血管病研究室）冠心病是多因素疾病，随着分子生物学技术的迅速发展，从基因水平探索冠心病的遗传本质已引起医学界的关注。大量的研究表明载脂蛋白基因或基因族的遗传变异如载脂蛋白ＡＩ／ＣⅢ、载脂蛋白Ｂ、...     

基因多态性与疾病相关性的遗传分析中某些值得注意的问题

绝大多数疾病的发生发展都是遗传因素与环境因素相互作用的结果,因此近年来从遗传学角度对致病基因(单基因病)和疾病易感基因(复杂性状多基因病)进行定位、鉴定和遗传流行病学的研究逐渐成为热点,国内外刊物发表相关的论文与日俱增.本文拟对该类研究中某些值得注意的问题作一讨论,以期抛砖引玉.     

医学遗传学课程教学改革探讨

现代医学认为，绝大多数疾病的发生、发展和转归都是遗传和环境综合作用的结果，人类所有疾病的发生、发展和转归都与遗传物质（DNA）的直接或间接变化相关。医学遗传学则是研究人类遗传性疾病的发生、发展和转归与遗传因素的关系，同时探讨疾病诊断、预防、治疗的遗传学方法及手段，以改善人类的健康水平的一门科学。由此可见，在现代医学的教育体系中，医学遗传学课程的教育、教学有着举足轻重的地位。     

临床遗传学新增二级学科研究生培养体系的设置与探讨

随着营养性和传染性疾病的明显减少,人们对人类疾病中遗传因素的决定作用愈加重视,社会对临床遗传医疗服务有着迫切的需求。通过近年来临床遗传学学科在国内外发展状况分析,阐述了该学科设置的意义与研究价值,同时介绍了临床遗传学的学科内涵与主要研究内容,并探讨了临床遗传学学科研究生培养目标及学位与课程体系的设置。     

常见空气污染的表观遗传效应研究进展

空气污染与多种疾病有关.近年来,越来越多的研究表明,表观遗传学修饰通常发生在疾病的早期,并且,与遗传学变化相比,表观遗传学修饰在疾病发生、发展中的作用更为重要.因此,对空气污染表现遗传效应的研究,能更全面地反映空气污染物与基因组的交互作用在疾病发生中的作用.同时,为减少高危人群空气污染的暴露及其引发的有害效应,空气污染的表观遗传学生物标志鉴定是采取及时有效预防措施的有力保证.     

表观遗传学与临床肾病

表观遗传学是研究不涉及DNA序列变化,表型却发生可遗传改变的一门不同于遗传学的学科,其异常可能影响疾病的发生发展。慢性肾脏疾病受到遗传因素和表观遗传修饰的双重影响。在一些临床肾脏疾病中,特别是一些特定基因的启动子区的甲基化水平异常可影响该基因的表达与失活,参与疾病的发生与发展。因此,通过对表观遗传学与临床肾脏疾病关系的研究,可为进一步认识和治疗某些临床肾脏疾病提供一种新的途径。     

吸烟和肺癌的遗传易感性

1951年．英国所有男医生都收到了来自Doll的邀请,共计40710人加入了一项为期5年的吸烟和非吸烟人群肺癌发病率的队列研究,1957年,英国医学研究委员会宣布：世纪初肺癌激增的始作俑者是吸烟,从而使“吸烟有害健康”写上了烟盒：1963年,Tokuhata等首次展示了遗传与肺癌休戚与共的关系,肺癌患者一级亲属增高2．5倍的肺癌发病率和吸烟无关。从此,吸烟、基因与肺癌的三角关系一直扑朔迷离。而近来一系列革命性的研究正在形成一句话“肺癌在本质上是一种基因病”。     

Clinical characteristics of patients with congenital long QT syndrome and bigenic mutations

Background Congenital long QT syndrome （LQTS） is an ion channelopathy associated with genetic mutations. It is well known that most LQTS patients （91%） have a single mutation. The purpose of this study was to investigate the clinical characteristics of congenital LQTS patients with bigenic mutations in Taiwan, China. Methods Congenital LQTS patients were recruited consecutively at Taiwan University Hospital in Taiwan from 2003 to 2009. The diagnosis of LQTS was defined by an LQTS Schwartz score greater than 4. Mutation screening in KCNQ1, KCNH2, KCNE1, and SCN5A was performed using direct sequencing. Results Three of 16 LQTS patients （18.7%） were identified with bigenic mutations. One patient had missense mutations in KCNQ1 and KCNH2, the second in KCNQ1 and KCNE1, and the third in KCNH2 and SCN5A. The mean age at onset of LQTS for patients with bigenic mutations was （17±3） years, and all of these patients were female. Two of them experienced seizure and one presented with syncope, although one of them had a family history of syncope. The mean QTc interval was （515＋17） ms, similar to those with single mutation or SNPs （（536~74） ms, P=-0.63）. Compared to those LQTS patients with single mutation or SNPs, a significantly higher percentage of LQTS patients with bigenic mutations presented with seizure and were younger at onset of the first index event （P=0.03 and 0.001, respectively）, but lower percentage of them presented with sudden cardiac death （P=0.03）. Conclusions Although the percentage of bigenic mutations in LQTS is less than 10% in Caucasian populations, we identified 3 of 16 LQTS patients （18.7%, 95% confidence interval： 0.04-0.46） with bigenic mutations in Taiwan. However, the sevedtv of their clinical presentations was not hioher than those patients with sinele mutation or SNPs.     

Effects of radiation-induced suicide gene therapy under radiation of radionuclide 125I on human hepatocarcinoma cells in vitro

There are few efficient therapeutic approaches to hepatocarcinoma.Chen et al1 developed iodine （131I） metuximab injection （Licartin）,a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody Fab＇2 fragment.HAb18G/CD147 is a hepatocellular carcinoma-associated antigen.But their results have no obvious improvements in survival rate of patients with hepatocarcinoma.Keywords：radiation effects; promoter regions, genetic lentivirus; cytosine deaminase; fluorocytosine; HepG2 cells     

Tumor necrosis factor gene polymorphisms and endometriosis in Asians: a systematic review and meta-analysis

Background Numerous studies have described the association between polymorphisms in the tumor necrosis factor （TNF） gene and risk of endometriosis.However,the results remain controversial.Here we reviewed studies reporting the association between TNF gene polymorphisms and endometriosis risk in Asians.Methods PubMed and Embase were searched.Twelve case-control studies assessing the role of multiple TNF gene polymorphisms in endometriosis were included.If no less than two articles evaluated one variant,meta-analysis was conducted; otherwise,narrative analysis was chosen.A fixed-or random-effects model was employed according to the heterogeneity among studies.The strength of the association between TNF gene polymorphisms and endometriosis risk was assessed by odds ratios and 95％ confidence intervals.Results For TNF-α-238G＞A,-308G＞A,-857C＞T,and-863C＞A,no significant associations were identified from all genetic models.For TNF-α-850T＞C,results from one study showed that patients harboring the heterozygote TC were less susceptible to endometriosis than patients harboring the homozygote TT.For TNF-α-1031T＞C,a mild increase in endometriosis risk was found in the Asian population.Meta-analysis from two studies found that the TNF-β ＋252＞G polymorphism had a protective effect in Chinese individuals.Due to the limitations of the included studies,it is necessitated to perform more studies to elucidate the possible roles of TNF gene polymorphisms in the pathogenesis of endometriosis.Conclusions TNF-α-1031T＞C and TNF-β ＋252A＞G were significantly associated with the risk of endometriosis in Asian and Chinese populations,respectively.To further evaluate these associations,more large-scale,rigorously designed studies are needed.     

Expression of human WFDC2 protein from patients with serous carcinomas by the two-tier system

The human WFDC2 protein,also known as human epididymal secretory protein 4 (HE4),is a new marker of tumor progression1 that is used for the differential diagnosis of ovarian cystadenocarcinomas.At present,the pathology of ovarian carcinomas is defined by the "dualistic model"2 and "heterogeneity of ovarian carcinomas"3 theories.Previously,it was considered that ovarian carcinomas originate from the ovaries themselves.The "dualistic model" assumes an external origin for ovarian carcinomas,in which it is considered that serous ovarian carcinomas originate from secondary implantation of oviduct mucosa epithelium.Epithelial ovarian carcinomas are not a single disease,but a set of "heterogeneous diseases".     

Genetic characterization and protein stability analysis of a Chinese family with Von Hippel-Lindau disease

Background Von HippeI-Lindau disease （VHL）,a heritable autosomal dominant disease characterized by neoplasia in multiple organ systems,has rarely been reported in Asia.We genetically investigated a unique Chinese family with VHL disease and performed an analysis of the VHL protein stability.Methods Genomic deoxyribonucleic acid （DNA） extracted from peripheral blood was amplified by polymerase chain reaction （PCR） to three exons of the VHL gene in 9 members of the Chinese family with VHL disease.PCR products were directly sequenced.We estimated the effects of VHL gene mutation on the stability of pVHL,which is indicated by the free energy difference between the wild-type and the mutant protein （△△G）.Results The Chinese family was classified as VHL type 1.Three family members,including two patients and a carrier,had a T to G heterozygotic missense mutation at nucleotide 515 of the VHL gene exon 1.This missense mutation resulted in the transition from leucine to arginine in amino acid 101 of the VHL protein.There was low stability of the VHL protein （the △△G was 12.71 kcal/mol） caused by this missense mutation.Conclusions We first reported a family with this VHL gene mutation in Asia.This missense mutation is predicted to significantly reduce the stability of the VHL protein and contribute to the development of the renal cell carcinoma （RCC） phenotype displayed by this family.The genetic characterization and protein stability analysis of families with VHL disease are important for early diagnosis and prevention of the disease being passed on to their offspring.     

Rosuvastatin escape in a Chinese elderly with hyperlipidemia

Statin is being used widely in patients who have hyperlipidemia,coronary arterial disease (CAD)or other atherosclerosis diseases.Analysis shows that lowering plasma low density lipoprotein cholesterol C (LDL-C) level depends on the dose and various statins treated.LDL-C will achieve the maximal effects after 7-10 days administration.1,2 Rosuvastatin is a hydrophilic statin,does not metabolize depending on cytochrome P 450 3A4,meaning less drug-drug interactions in cases of multipharmacy.     

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis： study protocol of a multicenter randomized controlled trial

BACKGROUND： Rheumatoid arthritis （RA）, as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA. METHODS AND DESIGN： This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1：1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo （imitation leflunomide）. The control group will receive leflunomide and an herbal placebo （imitation Xinfeng Capsule）. The American College of Rheumatology （ACR） Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate （ACR20）, which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment. DISCUSSION： The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is N CT01774877.