出生缺陷危险因素及诊断研究进展

出生缺陷正在成为婴儿死亡的主要原因,是目前全世界关注的一个重大公共卫生问题.出生缺陷可由遗传因素如染色体畸变、基因突变引起,也可由环境致畸因素或两者共同作用所致.我国出生缺陷发生率呈上升趋势.这些缺陷类型如果通过早期诊断、早期干预,其中至少70%可以避免.出生缺陷干预是一个系统工程,需要全社会参与.产前超声筛查和母体血清生化指标检测是胎儿出生缺陷干预的有效手段,是出生缺陷干预二级预防中的重要组成部分.     

肾移植受者硫嘌呤甲基转移酶基因多态性与硫唑嘌呤不良反应关系的研究

目的:探讨硫嘌呤甲基转移酶(thiopurine S-methyltransferase,TPMT)表型和基因多态性与硫唑嘌呤(AZA)所致不良反应的关系。方法:应用高效液相色谱法(HPLC)测定150例肾移植患者红细胞TPMT活性,采用等位基因特异性的PCR和限制性片断长度多态性的方法检测TPMT*2、*3A、*3B和*3C四种基因型,分析TPMT活性和基因多态性与AZA所致不良反应的关系。结果:30例(20%)患者由于发生了不良反应而停用AZA或减少了AZA的用量,其中12例患者发生了血液毒性,另外18例发生了肝脏毒性。将未发生不良反应的患者作为对照组,其红细胞TPMT活性范围为16.63~68.25 U,平均为(38.43±11.59)U。发生了血液毒性的患者红细胞TPMT活性平均为(24.16±9.84)U,明显低于未发生不良反应的患者(P=0.0003)。另外18例发生了肝脏毒性的患者TPMT活性离散度较大,与对照组比较差异无统计学意义(P=0.145)。本研究未发现TPMT活性缺乏者。共发现7例(4.7%)TPMT*3C杂合子患者,这7例患者均为TPMT中等活性13.04~19.21 U,平均为(...     

Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: A pilot study

The antidepressant activity of citalopram (R,S-CIT) is mainly due to its (S)-enantiomer (S-CIT). P-glycoprotein (P-gp), encoded by the ABCB1 gene, is a membrane transport protein which regulates the efflux of many drugs. Polymorphisms in the ABCB1 gene may have an impact on the expression and function of P-gp, thereby influencing the response to treatment with antidepressants, which are substrates of this protein. The influence of ABCB1 polymorphism on the disposition of R,S-CIT in plasma and cerebrospinal fluid (CSF) was examined under steady-state conditions in 15 patients with major depression treated with 40 mg/d R,S-CIT for 4 weeks. In contrast to the ABCB1 C3435T polymorphism, only the ABCB1 G2677T polymorphism significantly influences R,S-CIT plasma and CSF concentrations (46 ± 11 ng/ml versus 69 ± 20 ng/ml for TT versus GT/GG in plasma, p = 0.027; 24 ± 5 ng/ml versus 32 ± 9 ng/ml for TT versus GT/GG in CSF, p = 0.05). On the other hand, no significant influence of G2677T polymorphism was found on the plasma and CSF (S)/(R) ratio, suggesting a lack of stereoselectivity in the activity of this transporter. The 2677 GG/GT genotype was associated with a better treatment response (p = 0.001) compared with 2677TT genotype. Furthermore, higher R,S-CIT plasma and CSF concentrations were observed in treatment responders. This study is the first to demonstrate that a P-gp polymorphism significantly influences plasma and CSF concentrations of R,S-CIT in depressive patients, therefore possibly influencing the activity of this antidepressant. These findings should be replicated in future studies with larger groups of patients. Because of the small number of subjects in the present study, future studies with larger groups of patients, also with different ethnicities.     

AT1R、ACE基因多态性与东乡族原发性高血压的关系及其对降压药疗效的影响

目的：探讨血管紧张素转换酶（ACE）、血管紧张素Ⅱ（AngⅡ）Ⅰ型受体（ATIR）基因多态性与甘肃东乡族原发性高血压（EH）的关系。对不同基因型患者使用AT1R拮抗剂治疗，观察其疗效。方法：应用聚和酶链反应（PCR）方法检测汉族健康131例、东乡族健康102例、汉族EH198例、东乡族EH115例的AT1RA／C、ACE I／D基因多态性。随机选取60名EH患者，按其基因型分成AA和AC（AA、AC为基因型）两组，使用缬沙坦治疗8周，比较治疗前后血压变化。结果：ACE基因Ⅱ型在汉族EH组明显高于东乡族EH组（P〈0．05），ID基因型在东乡族EH组明显高于汉族EH组（P〈0．01）；AT1R基因AC型汉族EH组明显高于东乡族EH组（P〈0．05）；AA型在东乡族EH组明显高于汉族EH组（P〈0．05）。使用缬沙坦治疗8周，各基因型在治疗后患者血压均下降显著（P〈0．05）。不同基因型之间治疗后比较，降压效果无差异。结论：AT1R基因AA型和ACE基因ID型与东乡族EH有关；ACE基因Ⅱ型和AT1R基因AC型与汉族EH有关，C和D等位基因与汉族和东乡族EH无关。使用缬沙坦对不同基因型患者进行药物治疗，降压疗效相同，说明降压疗效与基因型无关。     

CD14基因多态性与术后严重感染易感性及预后的关系

目的 探讨内毒索受体CD14-1159C/T基因多态性与术后严重感染易感性及预后的关系.方法 以收治的42例术后严重感染患者为对象,以正常献血者为对照,提取全血基因组DNA,应用限制性长度片段多态性(RFLP)方法检测CD14-159C/T基因多态性,并研究CD14基因多态性与术后严重感染易感性及病死率的关系.结果 42例术后严重感染患者的T等位基因频率(78.4%)明显高于C等位基因频率(21.6%),且-159TT基因型患者病死率(84.6%)明显高于-159CT(15.4%)及-159CC患者(0)(P＜0.05).结论 CD14-159C/T基因多态性与术后严重感染的易感性及预后有一定关系.     

栽培黄连群体遗传关系的SRAP分析

目的揭示栽培黄连Coptis chinensis群体的遗传关系。方法以24个不同来源地的栽培黄连群体为试材,采用SRAP分子标记技术,用Treeconw软件分析遗传相似系数,UPGMA方法聚类,构建遗传系统树。结果36对引物共得到276条扩增条带,其中有120条呈现多态性,占43.48%,从DNA分子水平显示出供试种质遗传多样性并不丰富。遗传相似系数变化范围在0.877 0~0.951 9。聚类结果显示栽培黄连群体遗传关系与来源地无明显相关性,仅在小分支中表现出一定的地域相关性。结论栽培黄连群体的遗传多样性水平较低,显示遗传背景较为单一。     

Puumala hantavirus genetic variability in an endemic region (Northern Sweden)

Puumala hantavirus (PUUV), naturally harboured and shed by bank voles (Myodes [Clethrionomys] glareolus), is the etiological agent to nephropathia epidemica (NE), a mild haemorrhagic fever with renal syndrome. Both host and virus are found throughout much of the European continent and in northern Sweden NE is the second most prevalent serious febrile viral infection after influenza. The reliability of diagnostics by PCR depends on genetic variability for the detection of viral nucleic acids in unknown samples. In the present study we evaluated the genetic variability of PUUV isolated from bank voles in an area of northern Sweden highly endemic for NE. Genetic variability among bank voles was also investigated to evaluate co-evolutionary patterns. We found that the viral sequence appeared stable across the 80km study region, with the exception of the southernmost sampling site, which differed from its nearest neighbour by 7%, despite a geographical separation of only 10km. The southernmost sampling site demonstrated a higher degree of genetic similarity to PUUV previously isolated 100km south thereof; two locations appear to constitute a separate PUUV phylogenetic branch. In contrast to the viral genome, no phylogenetic variance was observed in the bank vole mtDNA in this study. Previous studies have shown that as a result of terrestrial mammals' postglacial re-colonization routes, bank voles and associated PUUV of a southern and a northern lineage established a dichotomous contact zone across the Scandinavian peninsula approximately 100-150km south of the present study sites. Our observations reveal evolutionary divergence of PUUV that has led to dissimilarities within the restricted geographical scale of the northern host re-colonization route as well. These results suggest either a static situation in which PUUV strains are regionally well adapted, or an ongoing process in which strains of PUUV circulate on a geographical scale not yet reliably described.     

有机阴离子转运多肽1B1遗传多态性对普伐他汀药动学的影响

 目的初步考察汉族人有机阴离子转运多肽1B1(OATP1B1)的遗传多态性及其对普伐他汀药动学的影响。方法考察180名汉族健康受试者SLCO1B1(OATP1B1的编码基因)的常见单体型(SLCO1B1^*1a,SLCO1B1^*1b,SLCO1B1^*5及SLCO1B1^*15),从中选择18名自愿参加且基因型为SLCO1B1^*1b/^*1b,SLCO1B1^*1a/^*15,SLCO1B1^*1b/^*15或SLCO1B1^*15/^*15的受试者入组药动学研究。分别在给药前及给予40 mg普伐他汀后0.33,0.67,1,1.5,2,3,4,5,6,8 h采集受试者血样至肝素抗凝管中。血浆普伐他汀浓度采用HPLC-UV测定。药动学参数应用WinNonlin 1.5软件中的非房室模型计算。SLCO1B1^*1b纯合子组受试者(n=9)和SLCO1B1^*15杂合子组受试者(n=8)药动学参数的统计学差异应用SPSS 10.0软件中的Mann-Whitney U检验评价。结果180名汉族人单体型SLCO1B1^*1a,SLCO1B1^*1b和SLCO1B1^*15的发生频率分别为0.294,0.614和0.092,未发现单体型SLCO1B1^*5;基因型SLCO1B1^*1a/^*1a,SLCO1B1^*1a/^*1b,SLCO1B1^*1b/^*1b,SLCO1B1^*1a/^*15,SLCO1B1^*1b/^*15及SLCO1B1^*15/^*15的发生频率分别为0.078,0.372,0.372,0.061,0.111及0.006。SLCO1B1^*1b纯合子组受试者(n=9)和SLCO1B1^*15杂合子组受试者(n=8)的ρ_max分别为(116.06±46.22)和(173.36±36.23)μg·L^-1,二者存在统计学差异(P=0.011<0.05)。2组受试者的其他药动学参数,如AUC_{0-8 h}(P=0.093>0.05),t_max(P=0.139>0.05),t_1/2(P=0.093>0.05)及CL/F(P=0.114>0.05)无统计学差异。值得注意的是,SLCO1B1^*15纯合子(n=1)的ρ_max和AUC_{0-8 h}在所有受试者中最高,分别为401.76μg·L^-1和660.05μg·h·L^-1;CL/F最低,为59.60 L·h^-1。结论180名汉族人OATP1B1存在遗传多态性,最常见的单体型为SLCO1B1^*1b。OATP1B1遗传多态性会对普伐他汀药动学产生影响。服用普伐他汀后,携带SLCO1B1^*15的受试者,尤其是SLCO1B1^*15纯合子受试者的血药浓度显著高于其他受试者。     

Bricolage in action: learning about,making sense of,and discussing,issues about genetically modified crops and food

Making sense of new technologies and their associated risks entails lay people in utilizing various modes of reasoning and making use of a range of interpretative resources at hand to interrogate evidence. Such sense making is accomplished collectively in ways that are sometimes playfully inventive, and which have regard to ideas of accountability and morally acceptability. In practice, such bricolage-like processes appear to have certain similarities with the work of everyday scientific investigation. This paper examines these processes of lay practical reasoning by adopting an analytic stance that is concerned with examining the fine detail of what people demonstrably do in accomplishing such work. It draws on data generated by number of reconvened discussion groups, which formed a component part of the recent public debate in the UK about the possible commercialization of genetically modified crops.     

华东地区汉族人群HB-1基因多态性的研究

目的:检测华东地区汉族人群HB-1基因的多态性,并与国外数据库进行比较。方法:采用直接测序法检测188例华东地区汉族正常个体全血标本中HB-1基因启动子、全部2个外显子及邻近的内含子区的多态性变化,所得结果与美国国立生物技术信息中心(NCBI)的SNP数据库(dbSNP)进行比较。结果:在188例正常样本中共发现6个SNPs,5个位于启动子,一个位于编码区,在dbSNP数据库中均已报道,但有6个数据库已报道的SNPs在本次研究中未能证实。结论:华东地区汉族人群HB-1基因多态性的分布与dbSNP数据库中的资料存在差异,为在华东地区汉族人群中研究HB-1基因相关疾病提供可靠数据。