TCF7L2、CDKAL1、SLC30A8和HHEX基因多态性与2型糖尿病微血管并发症的相关性

目的 研究TCF7L2、CDKAL1、SLC30A8和HHEX基因单核苷酸多态性(single nucleotide polymorphism,SNP)与2型糖尿病微血管并发症的相关性.方法 采用病例-对照方法分析研究对象[糖尿病视网膜病变组(diabetic retinopathy,DR)479例,糖尿病肾病组(diabetic nephropathy,DN) 248例,对照组650名]的TCF7L2基因rs7903146、rs6585205、rs11196218位点,CDKAL1基因rs10946398、rs4712527位点,SLC30A8基因rs13266634、rs3802177、rs11558471位点,HHEX基因rs1111875、rs7923837位点多态性与DR、DN发病风险的关系.结果 SLC30A8 rs11558471的等位基因及基因型频率在DR与对照组间差异有统计学意义(P＜0.05),等位基因A、基因型AA的OR值分别为1.27、1.68,TCF7L2 rs11196218的A等位基因在DN与对照组之间差异有统计学意义(P=0.0051,OR=1.37),但对P值做Bonferroni校正后差异无统计学意义.SLC30A8 rs13266634和rs3802177,CDKAL1 rs10946398,TCF7L2 rs6585205、rs7903146、rs11196218,HHEX rs7923837的等位基因及基因型频率在DR组与对照组间比较差异无统计学意义(P＞0.05),TCF7L2 rs6585205,CDKAL1 rs4712527,SLC30A8 rs13266634、rs3802177和rs11558471和HHEX rs7923837的等位基因和基因型频率在DN与对照组间差异无统计学意义,但是其相应的OR值都大于1.结论 SLC30A8基因多态性可能与DR发病相关;TCF7L2基因多态性可能与DN发病相关;不能排除CDKAL1、TCF7L2、HHEX基因多态性与DR的相关性及SLC30A8、CDKAL1、HHEX基因多态性与DN的相关性.     

肝脂酶基因启动子-250G/A多态性与2型糖尿病合并冠心病易感性的相关研究

目的 探讨汉族人群肝脂酶(hepatic lipase,HL)基因启动子-250G/A多态性与2型糖尿病(type 2 diabetes mellitus,T2DM)合并冠心病(coronary heart disease,CHD)的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法(polymerase chain reaction-restricted fragment length polymorphism,PCR-RFLP)检测364例T2DM+CHD组、357例T2DM组患者和356名健康对照者HL基因启动子-250G/A多态性,并分析其对脂类的影响.结果 T2DM组与对照组HL基因启动子-250G/A多态性基因型和等位基因频率差异无统计学意义(P>0.05);T2DM+CHD组GA+AA基因型频率低于对照组(0.431 vs 0.618,P=0.031);等位基因频率差异无统计学意义(P>0.05).调整混杂因素后,Spearman相关及线性回归分析,糖尿病患者(T2DM组和T2DM+CHD组),A等位基因与高密度脂蛋白胆固醇、载脂蛋白A1呈正相关;Logistic回归分析显示,A等位基因是冠心病发生的一个危险因素.结论 HL基因启动子-250G/A多态性与2型糖尿病合并冠心病的发生有关,并影响脂类代谢.     

VEGF基因单核苷酸多态性与中国北方汉族人SLE易感性的相关性研究

目的:研究血管内皮生长因子(VEGF)基因单核苷酸多态性(SNP)与中国北方汉族人系统性红斑狼疮(SLE)易感性的相关性。方法:应用Sequenom飞行时间质谱技术检测44例SLE患者和100例正常对照者外周血VEGF基因的SNPs,选择6个VEGF基因的SNP位点:rs2010963、rs3024994、rs3025000、rs3025010、rs3025035和rs833070进行基因分型,用SPSS 11.5软件对数据资料进行统计分析。结果:SLE患者VEGF多态性位点rs2010963、rs3024994、rs3025000、rs3025010、rs3025035的基因型频率及等位基因频率与正常对照组比较差异无统计学意义(P0.05);VEGFrs833070 A等位基因频率明显高于对照组(31.2%vs20%,χ2=4.547,P=0.033,OR=1.818,95%CI 1.045-3.162)。rs833070 G等位基因在SLE组中关节炎与无关节炎组中频率有显著差异(56%vs80.4%,χ2=5.613,P=0.018,OR=0.336,95%CI 0.134-0.843),rs833070 GG基因型频率明显低于无关节炎组(GGvsAG+AA:28%vs65.2%,χ2=6.684,P=0.010,OR=0.207,95%CI 0.061-0.705),而VEGF rs833070位点基因型、等位基因型的频率与患者血清中ds-DNA抗体、抗Sm抗体、狼疮性肾炎、间质性肺疾病的发生无相关性(P0.05)。结论:VEGF基因SNP点rs833070与北方汉族人SLE发病易感性相关,rs833070位点A等位基因可能增加了SLE患病的易感性,而rs833070 GG基因型及G等位基因型可能是SLE合伴关节炎的保护性基因。     

TNF-α单核苷酸多态性与中国北方汉族人类风湿关节炎的相关性研究

目的:研究肿瘤坏死因子α(TNF-α)基因单核苷酸多态性(SNP)与中国北方汉族人类风湿性关节炎(RA)易感性的相关性。方法:选取98例RA和100例正常对照者作为研究对象,应用Sequenom飞行时间质谱技术,对TNF-α基因的SNP点rs1800629(-308 A/G)、rs361525(-238 A/G)、rs1799724(-850 C/T)和rs1800610(+489 C/T)进行基因分型,用SPSS 11.5软件对数据资料进行统计分析。结果:RA患者TNF-α多态性位点rs1799724、rs1800610和rs361525的基因型频率及等位基因频率与正常对照组比较差异无统计学意义(P>0.05),而TNF-αrs1800629的基因型频率及等位基因频率与正常对照组比较有明显的统计学差异(P<0.05)。TNF-αrs1800629 G等位基因及GG基因型可以提高RA的发病风险性。结论:NF-α基因SNP位点rs1800629可能与北方汉族人RA发病易感性相关。     

has-miR-27a和has-miR-124a基因单核苷酸多态性与妊娠期糖尿病的相关性

目的 探讨has-miR-27a基因rs895819位点和has-miR-124a基因rs531564位点单核苷酸多态性(SNP)与妊娠期糖尿病(GDM)发病的相关性.方法 共纳入1 719例孕妇,其中GDM 839例;糖耐量正常和50 g葡萄糖负荷试验阴性者880例,作为对照组.采用TaqMan探针法检测两组孕妇SNP位点基因型,比较两组孕妇各SNP位点等位基因和基因型频率差异,以及不同基因型间临床生化指标的差异.结果 1)rs895819位点CC、CT和TT基因型频率在GDM组分别为3.1％、39.3％和57.6％,对照组分别为7.1％、37.6％和55.3％,CC基因型频率显著低于对照组(P＜0.05);隐性模型(CC vs CT +TT)中两组差异仍具有显著性[P=0.001;OR0.435(0.270,0.702)];GDM组C等位基因频率(22.8％)低于对照组(25.9％)(P＜0.05).2)rs895819 CC基因型孕妇空腹血糖低于CT +TT基因型孕妇(P＜0.05).结论 has-miR-27a基因rs895819位点与GDM相关,C等位基因降低GDM的发病风险.     

云南地区汉族人群PSMB8、PSMB9及TAP2基因多态性与类风湿关节炎的关联研究

目的 研究云南汉族人群中PSMB8、PSMB9及TAP2基因多态性与类风湿关节炎(rheumatoid arthritis,RA)的相关性.方法 应用聚合酶链反应-限制性片段长度多态性法对177例RA患者及288名健康对照PSMB8基因的rs2071543、rs55745125、rs138635403位点和PSMB9基因的rs17587多态性位点进行基因分型,应用多聚酶链反应扩增阻碍系统法对TAP2基因的rs2228396多态性位点进行基因分型.计算基因型及等位基因频率.采用Epi Info 7软件计算上述多态位点在RA组及正常对照组之间的比值比(OR值).结果 rs138635403及rs17587位点的等位基因及基因型频率在RA组和对照组间差异有统计学意义(P＜0.05),其中RA组rs17587的GG基因型频率(0.672)高于对照组(0.524)(OR=1.862,95％CI:1.261～2.749).结论 云南汉族人群PSMB9基因的rs17587位点多态性与RA存在关联.     

2型糖尿病及其肾病与血管生成素2基因多态性的关联分析

目的 研究2型糖尿病(type 2 diabetes mellitus,T2DM)及其肾病(diabetic nephropathy,DN)发生、发展与血管生成素2(angiopoietin-2,Ang-2)基因多态性的关联性.方法 应用等位基因特异聚合酶链反应检验无亲缘关系汉族人群的2型糖尿病及其肾病患者221例、正常对照104名Ang-2基因单核苷酸多态性(single nucleotide polymorphism,SNP)759T/G、1078A/G、1233A/G在病例组中的频率,并用尿白蛋白排泄率、炎症标志物单核细胞趋化蛋白浓度变化探讨上述SNP与T2DM、DN发生发展的关联.结果 (1) Ang-2 759 T/G、1078 A/G基因型频率和等位基因频率在各组中的差异无统计学意义,而1233 A/G基因型频率和等位基因频率的差异有统计学意义(P＜0.05);(2)在校正年龄和性别等因素后,1233A/GSNP G等位基因患T2DM和DN的风险分别是A等位基因的2.265倍(95％ CI:1.223～1.402,P=0.031)和1.789倍(95％ CI:0.889～1.021,P=0.012);(3) Ang-2 1233A/G G等位基因与DN发生相关(r=1.321,OR=1.427,95％ CI:2.324～4.177,P=0.034).结论 Ang-2 1233A/G SNP与2型糖尿病的发生有关;AG+ GG基因型和等位基因G可能是DN发生、发展的风险因素.     

白细胞介素1α基因单核苷酸多态性与甲型H1N1流感易感性的关系

目的 探讨白细胞介素1d(IL-1α)基因单核苷酸多态性(SNP)与甲型H1N1流感易感性的关系.方法 从IL-1α基因启动子区域中选取4个SNP位点rs1800587、rs2856836、rs2856838、rs3783525,针对以上位点建立基于飞行时间质谱分析技术(TOF-MS)鉴定SNP的方法,对167例H1N1流感患者(H1N1组)和192例健康对照人群(对照组)进行检测.确定各SNP位点的等位基因和基因分型;对比两组等位基因和各基因型的频率.结果 rs1800587、rs2856836、rs2856838位点具有T和C两种等位基因,包括TT、TC、CC 3种基因型.rs3783525具有A和T两种等位基因,包括AA、AT和TT3种基因型.H1N1组和对照组rs 1800587位点的等位基因频率差异有统计学意义(x2=12.69,P=0.000,OR=2.424,95％CI=1.472 ～ 3.993),rs2856836,rs2856838,rs3783525等位基因频率在H1N1组和对照组中差异则无统计学意义.H1N1组rs1800587位点CC纯合子频率低于对照组[72.5％(121/167)比87.0％(167/192),P＜0.05],杂合子(TC)频率高于对照组[25.1％(42/167)比12.5％(24/192),P＜0.05],而两组TT纯合子频率差异则不具有统计学意义.H1N1组rs2856836位点杂合子(TC)频率高于对照组[25.7％(43/167)比17.2％(33/192),P＜0.05],TT基因型与CC基因型频率在两组间差异均没有统计学意义.rs2856838位点对照组TT纯合子频率低于H1N1组[4.2％(8/192)比10.8％(18/167),P＜0.05],其余2种基因型TC与CC在两组间差异没有统计学意义.H1N1组rs3783525位点TTT纯合子频率高于对照组[21.0％ (35/167)比13.0％(25/192),P＜0.05],两组间的另两种基因型TC与CC差异也没有统计学意义.结论 IL-1α基因多态性位点rs1800587、rs2856836、rs2856838、rs3783525与甲型H1N1流感易感性相关.     

ESR1基因单核苷酸多态性及单倍型与精神分裂症的关联研究

目的 探索雌激素受体1 (estrogen receptor 1,ESR1)基因rs2234693、rs9340799和rs3798759位点单核苷酸多念性(single nucleotide polymorphisms,SNPs)及其单倍型与精神分裂症(schizophrenia,SZ)发病之间的相关性.方法 应用聚合酶链反应-限制性片段长度多态性技术对333例SZ患者和315名正常对照rs2234693、rs9340799和rs3798759位点进行基因分型,应用x2检验对SZ组和对照组等位基因、基因型和单倍型频率进行分析.结果 rs2234693、rs9340799位点两组间基因型频率及等位基因分布差异均无统计学意义(P＞0.05).SZ组rs3798759位点GG基因型频率及G等位基因频率均高于健康对照组(P＜0.01).性别分层分析提示,女性SZ患者rs3798759位点TG、GG基因型频率及G等位基因频率均高于健康女性(P＜0.05).单倍型C-A-G和C-G-G在SZ组的分布频率高于对照组(P＜0.05).结论 rs3798759位点突变可能为女性精神分裂症发生的风险因子,C-A-G和C-G-G单倍型可能为精神分裂症的遗传风险单倍型.     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Intestinal helminthiasis in school children in Haiti in 2002

A survey on intestinal helminths in school children was conducted in Haiti in 2002. This first nationwide study involving the entire country was stratified by department according to urban and rural zones using the cluster method. Focusing on elementary school children (n=5792; age range 3 to 20 years), it involved 26 urban and 49 rural schools randomly selected. Stools were preserved in formalin and examined by the Ritchie technique. Thirty-four per cent of stools (1981/5792) tested positive for intestinal helminths with the following parasites identified: Ascaris lumbricoides (27.3%), Trichuris trichiura (7.3%), Necator americanus (3.8%), Hymenolepsis nana (2%), Taenia sp. (0.3%) and Strongyloides stercoralis (0.2%). The helminth prevalence was higher in rural (38.4%) compared to urban areas (30%). There was no significant difference in prevalence by sex and age. The importance of geohelminths changed from one department to another with the highest prevalence found in the Southern department of Grande Anse (73.7%) and the lowest prevalence in the Center department (20.6%). Five out of the country's nine departments had a similar prevalence varying from 25.5% to 28.2%. Intestinal helminthic polyparasitism was observed in a percentage of infested school children comprise between 3.4% and 28.6% according in relation to the geographical area. A program to fight against geohelminths in school children should be initiated as a public health priority. Albendazole is the drug of choice. Frequency of drug distribution should be based on the prevalence of geohelminths in each department.     

Experience in adult population in dengue outbreak in Delhi

A dengue outbreak has recently hit the Indian capital. We studied the clinical profile of adult patients. Five hundred and sixty patients of dengue infection were admitted in a specially created ward according to the criteria laid down by WHO. Haematemesis (28.28%), epistaxis (26.78%) and malena (14.28%) were some of the common presentations. Similarly lymphadenopathy, especially cervical (30.89%), palatal rashes (26.96%) and hepatomegaly (23.75%) were the most commonly encountered findings on physical examination. Most of the cases were of dengue fever with haemorrhage and only 2.5% cases were classified under dengue haemorrhagic fever or dengue shock syndrome. The average hospital stay was 3.4 days but only 9.8 hours in the eleven patients who died, suggesting their late arrival in preterminal situation giving little time for resuscitation. Thrombocytopenia was not a feature and only 12.85% patients had platelet count less than 70,000/cmm. Most of the patients who were admitted with thrombocytopenia, showed normalization in their platelet counts in next few days. Serological examination demonstrated evidence of recent dengue infection in 41.17% patients. Few patients required blood or platelet concentrate transfusion. Eleven patients died, three due to DIC, one of intracranial haemorrhage and seven due to massive gastric haemorrhage. Rest of the patients recovered completely. Thus we can conclude that recent outbreak in Delhi was of dengue fever with haemorrhage and mortality was very low in patients who came early to the hospital.     

Changes in the hypothalamic nuclei in in experimental allergy

Summary In rabbits subjected to prolonged sensitization and in which the Arthus phenomenon was induced there was a marked reaction of the hypothalamic nuclei. Staining by Gomori's method indicated a cellular swelling, loss of granules, and protoplasmic vacuolization in the supraoptic nucleus. There was a considerable increase in the size of the cross-sectional area of the cells. The same effects were much less well shown in the paraventricular nucleus. These results show that marked signs of increased neurosecretion developed in the animals at the height of the Arthus phenomenon.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten Éksperimental'noi biologii i Meditsiny, Vol. 55, No. 4, pp. 110–113, April, 1963.     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.