GSTO基因多态性与燃煤污染型砷中毒易感性的关系

[目的]探讨GSTO基因多态性与燃煤污染型砷中毒易感性的关系.[方法]应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测130名燃煤型砷中毒患者和140名健康个体GSTO1 Ala140Asp和GSTO2Asn142Asp基因两个位点的多态性,并分析不同基因型与砷中毒发病风险的关系.[结果]病例组中携带GSTO2 142Asn/Asp Asp/Asp(杂合型 突变纯合型)基因型个体的比例显著高于对照组,携带该基因型的个体较携带GSTO2 142Asn/Asn(野生纯合型)基因型个体发生砷中毒的风险升高1.18倍(ORadj=1.18,95%CI:1.02～1.37);而病例组中携带GSTO1140Ala/Asp Asp/Asp(杂合型 突变纯合型)基因型个体的比例仅略高于对照组,差异无统计学意义(ORadj=0.98,95%CI:0.51～1.91);但同时携带GSTO1 140Ala/Asp Asp/Asp和GSTO2 142Asn/Asp Asp/Asp基因型的个体砷中毒的发病风险显著增加(ORadj=2.48,95%CI:1.14～5.40).[结论]携带GSTO2Asn142Asp基因型个体有较高的砷中毒发病风险;而同时携带GSTO1 140Ala/Asp Asp/Asp和GSTO2 142Asn/Asp Asp/Asp的个体可能更容易发生砷中毒.     

GSTO1基因多态性与新疆饮水型地方性砷中毒的关联研究

目的探讨GSTO1基因多态性与饮水型地方性砷中毒易感性的关系。方法对新疆奎屯砷中毒病区慢性砷中毒患者96人,病区内对照组73人,以及非病区外对照组89人,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对GSTO1基因rs4925及rs11509438多态位点进行检测,用聚合酶链反应-双对引物多态性(PCR-CTPP)方法对GSTO1基因rs11509437位点进行检测,分析不同基因型与砷中毒发病风险的关系。结果 GSTO1基因rs4925、rs11509438及rs11509437位点的基因型以及等位基因频率在三组间的分布差异均无统计学意义(P0.05),GSTO1基因rs4925、rs11509438及rs11509437位点的基因多态性在不同砷暴露人群中的发病风险,差异均无统计学意义(P0.05)。结论 GSTO1基因rs4925、rs11509438及rs11509437位点可能与新疆饮水型地方性砷中毒无关联。     

X线修复交叉互补基因1多态性与1,3-丁二烯致接触工人染色体损伤易感性关系的研究

目的探讨DNA损伤修复基因X线修复交叉互补基因1(XRCC1)多态性在1,3-丁二烯致外周血淋巴细胞染色体损伤易感性中的作用。方法采用胞质分裂阻滞微核试验方法(CB-MN)评价166名1,3-丁二烯接触工人和41名正常人染色体损伤水平,应用聚合酶链反应-限制性片段多态性技术(PCR-RFLP)对接触工人第19染色体上的XRCC1第6外显子194密码子,第9外显子280密码子和第10外显子399密码子进行多态性检测。结果接触组和对照组的微核发生率分别为(3.39±2.42)‰和(1.48±1.26)‰,差异有显著性(P0.01)。高剂量接触组工人比低剂量接触组工人更容易发生染色体损伤(FR=1.30,95%CI1.14～1.53,P0.05)。XRCC1194突变基因携带个体的微核发生率比野生纯合型个体显著增高(FR=1.13,95%CI1.07～1.27,P0.05);XRCC1280突变纯合型个体的微核率较野生纯合型显著增加(FR=1.67,95%CI1.10～2.42,P0.05);XRCC1399杂合型个体以及杂合型和突变纯合型个体的微核率均显著增加(FR=1.26,95%CI1.03～1.53;FR=1.24,95%CI1.03～1.49,P0.05)。CAG/TGG双体型个体微核率显著降低,结论 XRCC1194、280、399突变位点携带工人染色体损伤风险增高。     

HO-1基因BccⅠ位点多态性与职业性慢性锰中毒易感性关系的病例对照研究

目的 探讨血红素加氧酶-1( HO-1)基因BccⅠ位点多态性与职业性慢性锰中毒遗传易感性的关系.方法 采用1∶2配对病例-对照研究的方法,应用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)测定200例职业性慢性锰中毒患者与400例对照组HO-1基因BccⅠ位点基因型,统计分析基因多态性与职业性慢性锰中毒的关系.结果 未发现突变纯合基因型;HO-1基因BccⅠ位点等位基因及基因型在对照组和病例组中分布差异无统计学意义;在男性病例组与对照组中的分布差异亦无统计学意义;但分层分析后发现在工龄20 ～ 29 a的对照组和病例组中,等位基因S携带者发生职业性慢性锰中毒的危险性为R的2.632倍(95％ CI=1.210～5.724),携带基因型RS的个体患职业性慢性锰中毒的危险性是携带基因型RR个体的2.788倍(95％ CI=1.251～6.216).结论 未发现HO-1基因BccⅠ位点基因多态性与职业性慢性锰中毒的易感性有关,但发现在工龄20 ～29 a的人群中携带S等位基因或具有RS基因型的个体发生职业性慢性锰中毒的危险性增加.     

CYP1B1基因多态性与异常体液型乳腺癌易感性

目的 探讨细胞色素氧化酶p450(cytochrome,CYP)1B1基因外显子3密码子432亮氨酸(Leu)-缬氨酸(Val)位点多态性与乳腺癌(BC)及其异常体液型乳腺癌(BCAH)的相关性.方法 按维吾尔医学将乳腺癌病例组分为4种体液型,应用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术检测84例BC患者和131例对照组的CYP1B1基因Leu432Val位点多态性的分布频率.结果 CYP1 B1各基因型及等位基因分布频率在BC、BCAH与对照组之间差异均无统计学意义(P＞0.05);在BC病例组中Leu/Val和Val/Val合并后其发生BC的风险是野生型Leu/Leu个体的2.137倍(95%CI=0.969 ～4.717,P=0.056),在BCABH病例组中其发生BC的风险是野生型Leu/Leu个体的3.636倍(95% CI =0.996～13.157,P=0.062).结论 CYP1B1突变基因型(Leu/Val+ Val/Val)可能与新疆汉族人群BC和BCABH易感性有关.     

硫酸基转移酶SULT1E1、SULT1A1基因多态性与子宫平滑肌瘤易感性的关联研究

目的:探讨硫酸基转移酶SULT1E1、SULT1A1基因多态性对子宫平滑肌瘤易感性的影响。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析法检测子宫平滑肌瘤组和对照组SULT1E1基因rs3736599位点、SULT1A1基因rs9282861位点的多态性情况。结果:①病例组和对照组SULT1E1 rs3736599位点基因型分布差异有统计学意义(P=0.032),携带突变A等位基因(基因型为A/A和A/G)女性发生子宫平滑肌瘤的风险是野生型纯合子G/G女性的3.497倍(P=0.034,OR=3.497,95%CI:1.12～10.91)。②病例组和对照组SULT1A1 rs9282861位点基因型分布差异无统计学意义。结论:硫酸基转移酶SULT1E1基因rs3736599多态性可能与子宫平滑肌瘤易感性相关,携带突变A等位基因可能是子宫平滑肌瘤的危险因素。     

低密度脂蛋白受体1基因多态性与Hp感染后胃癌易感性的关联

目的 探讨低密度脂蛋白受体1(LPR1)基因多态性与幽门螺杆菌(Hp)感染后胃癌易感性的关联。方法2018年1月-2020年1月北京医院收治的胃癌患者180例为病例组,根据Hp免疫球蛋白(Ig)G抗体检测结果,将其分为Hp阳性组、阴性组;另选同期年龄匹配的健康体检者40名为对照组,采用聚合酶链反应(qPCR)检测LPR1 rs688、rs5925、rs11172113和rs2228671位点的基因多态性,采用单因素和多因素Logistic回归模型分析LPR1基因多态性与Hp感染后胃癌易感性的关系。结果 病例组LPR1基因rs688位点CC基因型及C基因频率分布均于高于对照组(P<0.05),Logistic回归模型分析结果显示,rs688 CC基因型(OR=1.246)、携带rs688 C等位基因(OR=2.337)是影响胃癌发生的危险因素(P<0.05)。在位点rs688,Hp感染阳性组携带CC基因型频率、C基因频率高于Hp阴性组(P<0.05),Logistic回归模型分析结果显示,rs688 CC基因型(OR=3.245)、携带rs688 C等位基因(OR=3....     

DNA修复基因hOGG1多态性、HBV感染交互作用与肝细胞癌易感性的关系

目的 探讨广西肝癌高发区人群DNA修复基因8-羟基鸟嘌呤糖苷酶1单核苷酸多态性与肝细胞癌易感性的关系,并分析与环境危险因素的交互作用.方法 采用以医院为基础的病例-对照研究,对广西壮族自治区500例肝细胞癌和507例正常对照进行流行病学调查,并应用TaqMan MGB荧光定量PCR方法检测hOGG1-Ser326Cys位点基因型.结果 病例组和对照组中hOGG1-326Cys突变等位基因分布频率为24.60％和10.75％ (P ＜0.05);该位点3种基因型Ser/Ser、Ser/Cys和Cys/Cys在病例组和对照组中分布频率分别为71.40％、8.00％、20.60％和84.22％、10.06％、5.72％ (P ＜0.05);与携带hOGG1基因326位点野生纯合子Ser/Ser基因型者比较,携带至少一个hOGG1-326Cys突变等位基因的个体患肝癌风险显著增加(OR=2.14,95％CI:1.57 ～2.91);交互作用分析结果表明hOGG1基因326位点多态性与慢性HBV感染之间在肝细胞癌发生中具有交互作用,相乘模型交互作用指数为0.61,相加模型交互作用指数为1.31.结论 hOGG1-326Cys突变等位基因是肝细胞癌发生的危险等位基因;携带至少一个hOGG1-326Cys突变等位基因的个体若同时暴露于HBV慢性感染,患肝癌的风险显著增加.     

CYP1A1和CYP2E1基因多态性与燃煤型砷中毒发病风险关系

目的探讨CYP1A1基因和CYP2E1基因多态性与燃煤型砷中毒发病风险的关系。方法以130例燃煤型砷中毒患者为病例组, 以140名健康居民为对照组, 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测CYP1A1 Msp I、CYP2E1 Dra I和 CYP2E1 Pst I位点基因多态性, 并进行基因联合作用分析。结果CYP1A1基因 Msp I位点 m1/m1(纯合野生型) 基因型和m1/m2+m2/m2(杂合型+纯合突变型)基因型在病例组和对照组的分布频率分别为34.2%、65.8%和30.9%、69.1%; CYP2E1基因 Pst I位点 c1/c1(纯合野生型) 基因型和c1/c2+c2/c2(杂合型+纯合突变型)基因型在病例组和对照组的分布频率分别为62.6%、37.4%和57.4%、42.6%;CYP2E1基因 Dra I位点 DD(纯合野生型) 和DC+CC(杂合型+纯合突变型) 基因型在病例组和对照组的分布频率分别为58.7%、41.3%和61.4%、42.6%;上述3个多态位点各基因型在两组间的分布差异无统计学意义(P=0.341、0.574、0.972)。未发现CYP1A1 Msp I、CYP2E1 Pst I和 CYP2E1 Dra I多态位点与燃煤型砷中毒的发病风险存在统计学关联(P_校正= 0.433、0.219、0.832);上述多态位点各基因型之间未发现存在联合作用。结论CYP1A1和CYP2E1基因多态性与燃煤型砷中毒的发病风险无关。     

白介素-1A（IL-1A）和IL-1B基因多态性与冠心病关系的病例-对照研究

[目的]研究白介素-1A（inter／eukin-1A,1L-1A）和IL-1B基因多态性与冠心病（CHD）的关系。[方法]采用病例一对照研究,按照WHO的CHD诊断标准,选取CHD病例1003人,年龄和性别频率匹配的对照1003人。使用标准化的调查表获得研究对象的基本资料;采用ABI7900HT的Taqman基因分型技术检测基因多态性。[结果]IL-1A基因外显子上的多态性位点rs17561（ala114ser）与CHD有关。与GG相比,携带刀基因型者患CHD的危险性为GG的3倍。未发现IL-1B基因上的4个多态性位点（SNPs）与CHD有关。进一步的单倍型研究显示单倍型在CHD组和对照组差异没有统计学意义。[结论]基因IL-1A上的多态性位点rs17561与CHD有关,IL-1B上的4个SNPs与CHD无关。     

H1N1 vaccination

Early results (January to April) from the 2010 Canadian Community Health Survey show that an estimated 41% of Canadians (excluding those in the territories) aged 12 or older had been vaccinated for H1N1 by April 2010. The percentages were higher in the Atlantic provinces, Quebec and Saskatchewan than in Canada overall. Relatively high percentages of females and people aged 45 or older were vaccinated; the percentage of immigrants who had done so was relatively low. Being in a priority group (health-care worker, having children younger than 5 in the household, or having a chronic condition that could increase the risk for complications from H1N1) increased the likelihood of vaccination. A history of seasonal flu vaccination and having a regular doctor were also associated with H1N1 vaccination. Nearly three-quarters of those who had not been vaccinated reported that they did not think it was necessary.     

被动吸烟与cyp1b1、gstp1、sult1a1基因多态性对乳腺癌发病的影响

目的 探讨被动吸烟、cyp1b1、gstp1、sult1a1基因多态性及其联合作用对乳腺癌发病的影响。方法 2014 - 2015年间,采用病例-对照研究方法,收集病例794例,对照805例。问卷调查收集研究对象信息。采用飞行质谱技术,进行cyp1b1、gstp1、sult1a1基因单核苷酸多态性分型检测。采用多因素非条件 logistic 回归,分析环境烟草烟雾暴露及cyp1b1、gstp1、sult1a1基因多态性与乳腺癌发病风险的关系。结果 调整年龄、教育程度、家庭年总收入、职业、婚姻状况后,环境烟草烟雾暴露与gstp1基因多态性未发现协同作用。以环境烟草烟雾低暴露且携带 cyp1b1 rs1056836 C等位基因为参照,环境烟草烟雾高暴露且携带 GG 基因在绝经前女性中乳腺癌风险明显增高（OR = 1.678,95%CI:1.039～2.711）。以环境烟草烟雾组合低暴露且携带sult1a1 rs9282861GG基因型为参照,环境烟草烟雾高暴露且携带A等位基因绝经前乳腺癌风险明显增高（OR = 2.389,95%CI:1.157～4.931）,但交互作用系数无统计学意义。结论 环境烟草烟雾高暴露与cyp1b1 及sult1a1基因对乳腺癌发病风险可能存在协同作用,但尚扩大样本进行验证。     

Echo-AM1-1 encephaloscope]

A new miniature model of the A-mode ultrasonic echoencephaloscope, 0.88 MHz, has been developed and adopted to practical use in neurology. The device contains a detector for amplitude determination of echopulsation and curve (echopulsograms) recording. It is highly sensitive, cost-effective, which enhances the quality of rapid diagnosis of central nervous diseases, including those of vascular genesis, in in- and outpatient settings.     

接种甲型H1N1流感疫苗后患甲型H1N1流感分析

目的 分析接种甲型H1N1流感疫苗后发生甲型H1N1流感感染的病例,探讨发病原因,为进一步提高疫苗预防效果提供参考依据.方法 对接种甲型H1N1流感疫苗后发生甲型H1N1流感感染148例,进行回顾性调查分析.结果 接种甲型H1N1流感疫苗11176例.发生甲型H1N1感染148例,感染率1.32%,其中1～14 d感染81例,感染率0.72%,＞15 d感染67例,感染率0.60%.结论 甲型H1N1流感病毒裂解疫苗是一种安全高效的疫苗,不足之处尚待进一步探讨、完善.     

NF1 gene and neurofibromatosis 1

Neurofibromatosis 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant condition caused by mutations of the NF1 gene, which is located at chromosome 17q11.2. NF1 is believed to be completely penetrant, but substantial variability in expression of features occurs. Diagnosis of NF1 is based on established clinical criteria. The presentation of many of the clinical features is age dependent. The average life expectancy of patients with NF1 is probably reduced by 10-15 years, and malignancy is the most common cause of death. The prevalence of clinically diagnosed NF1 ranges from 1/2,000 to 1/5,000 in most population-based studies. A wide variety of NF1 mutations has been found in patients with NF1, but no frequently recurring mutation has been identified. Most studies have not found an obvious relation between particular NF1 mutations and the resulting clinical manifestations. The variability of the NF1 phenotype, even in individuals with the same NF1 gene mutation, suggests that other factors are involved in determining the clinical manifestations, but the nature of these factors has not yet been determined. Laboratory testing for NF1 mutations is difficult. A protein truncation test is commercially available, but its sensitivity, specificity, and predictive value have not been established. No general, population-based molecular studies of NF1 mutations have been performed. At this time, it appears that the benefits of population-based screening for clinical features of NF1 would not outweigh the costs of screening.     

GSTM1及GSTT1和GSTP1基因多态性对尿中1-羟基芘水平的影响

目的 研究GSTM1、GSTT1和GSTP1基因多态性对多环芳烃接触工人尿中1-羟基芘(1-OHP)水平的影响.方法 分别选取2个炼焦厂共447名多环芳烃职业接触工人(接触组)和某线材厂220名非职业接触工人(对照组)作为研究对象,采用高效液相色谱法测定尿中1-OHP水平,采用线性回归统计模型分析GSTM1和GSTT1缺失型及GSTP1 I105V位点的多态性对不同人群尿中1-OHP水平的修饰作用.结果 接触组工人尿中1-OHP浓度为4.61 μmol/mol Cr,明显高于对照组(0.34μmol/mol Cr),差异有统计学意义(P＜0.05).接触类别和吸烟分别是影响尿中1-OHP水平的主要因素,在控制各混杂因素的影响后,线性回归分析显示,接触组尿中1-OHP水平和GSTP1 I105V位点多态性有关(单基因分析,P=0.012;多基因分析,P=0.011),对总体样本,单基因模型和多基因模型均显示,尿中1-OHP水平可能和GSTT1缺失型多态有关(P=0.055),多基因交互作用分析显示,GSTT1和GSTP1基因多态对接触组尿中1-OHP水平具有交互作用.结论 谷胱甘肽硫转移酶(GSTs)基因的多态性对接触多环芳烃工人尿中1-OHP水平有影响.

Abstract：

Objective To investigate the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-hydroxypyrene (1-OHP) excretions in workers under different exposure levels. Methods Four hundred and forty-seven occupationally exposed workers from two coking plants and 220 control workers from a wire rod plant were genotyped to analyze the modification of GSTM1, GSTT1 and GSTP1 gene polymorphisms on urinary 1-OHP excretions. Results The urinary 1-OHP concentration in exposed group was much higher than that in control group (4.61 vs 0.34 μmol/mol Cr, P＜0.05). Occupational exposure levels and cigarette smoking were of the dominating factors affecting 1-OHP excretions in urine. After controlling potential confounders, decreased excretion of urinary 1-OHP was associated with GSTP1 I105V AG + GG genotype in coke oven workers (single-gene model, P=0.012; multi-gene model, P=0.011 ) and with GSTT1 null type in the analysis including all subjects (P=0.055 in both single-gene and multi-gene models). GSTT1 and GSTP1 were interacted on the urinary concentrations of 1-OHP. Conclusion Urinary 1-OHP concentrations can be modified by GSTM1, GSTT1 and GSTP1 gene polymorphisms, indicating that these genes are involved in the metabolism of polycyclic aromatic hydrocarbons.     

Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China

The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China.