血脂水平、ApoE和SLCO1B1基因多态性与晚期支架内再狭窄的相关性研究

目的 对比分析晚期支架内再狭窄(in-stent restenosis, ISR)与无ISR患者的临床特点、血脂水平、载脂蛋白E (apolipoprotein E, ApoE)以及SLCO1B1基因的多态性,探讨影响晚期ISR的临床危险因素。方法 入选2018年1月至2020年12月住院行冠状动脉造影证实晚期ISR的患者共61例,另外入选行冠状动脉造影证实无晚期ISR的患者共119例为对照组。比较两组的临床特点、血脂水平以及ApoE以及SLCO1B1基因的多态性。所有患者根据低密度脂蛋白胆固醇（low-density lipoprotein cholesterol, LDL-C）水平分为＜1.4mmol/l组,1.4~1.8 mmol/L组以及＞1.8 mmol/L组,=比较不同组别晚期ISR的发生率。结果 晚期ISR组与无ISR组患者ApoE、SLCO1B1基因型以及等位基因的频率并无统计学差异（P＞0.05）,将不同基因型和等位基因频率分别进行组内两两对比,结果也无统计学差异（P＞0.05）。两组患者总胆固醇(total cholesterol ,TC)、LDL-C、载脂蛋白B(apolipoprotein B, ApoB)、ApoB/ApoA比值以及非高密度脂蛋白胆固醇（non-high-density lipoprotein cholesterol, n-HDL-C）水平均有统计学差异,晚期ISR组上述指标均比对照组偏高（P<0.05）。3. ＜1.4 mmol/L组的ISR发生率为17.9%,1.4~1.8mmol/l组的ISR发生率为31.3%,＞1.8 mmol/L组的ISR发生率为39.4%。不同LDL-C水平的组间总体ISR发生率并无统计学差异（P＞0.05）。进一步行组间两两对比,小于＜1.4mmol/l组的ISR发生率为与＞1.8mmol/l组的ISR发生率有差异（P<0.05）。 结论 冠状动脉支架术后的患者,其ApoE或SLCO1B1的基因多态性与晚期ISR的发生率无明确关系。晚期ISR患者血脂水平较无ISR患者升高明显,将LDL-C降至1.4mmol/l以下可能有助于减少晚期ISR的发生。     

药物洗脱支架置入治疗不同时期冠状动脉支架内再狭窄对比研究

目的 比较药物洗脱支架(DES)治疗早期(≤1年)、晚期(＞1年)支架内再狭窄病变(ISR)患者的长期临床疗效。方法 收集2008年10月至2011年12月在北京安贞医院因ISR接受DES置入治疗并完成临床随访的患者资料,根据DES术后发生ISR的时间是否大于1年分为早期ISR组与晚期组。比较两组组患者术后1年的主要不良心血管事件［MACE,包括全因死亡、心肌梗死(MI)和靶病变再次血运重建(TLR)］。结果 早期ISR组入选患者80例,晚期ISR组入选患者124例。早期ISR组不稳定型心绞痛发生率明显低于晚期ISR组,差异有统计学意义(27.5%对63.7%,P<0.01);其余基线资料差异无统计学意义(P>0.05)。两组在病变部位、病变类型、病变长度方面比较差异均无统计学意义(P>0.05)。早期ISR组MACE发生率明显高于晚期ISR组(30%对15.3%,P<0.01),其中早期ISR组TLR明显高于晚期ISR组,差异有统计学意义(26.3%对12.1%,P<0.01)。结论 DES治疗ISR患者安全有效,但治疗早期ISR组病变TLR发生率高于晚期ISR组。     

药物洗脱支架治疗冠状动脉支架内再狭窄和冠状动脉原发病变的随访研究

目的:比较药物洗脱支架(DES)治疗早期(≤1年)、晚期(1年)支架内再狭窄病变(ISR)与冠状动脉原发病变(De novo)患者的长期临床疗效。方法:收集自2008年10月至2011年12月,北京安贞医院因ISR接受DES置入治疗并完成临床随访的患者资料,根据DES术后发生ISR的时间是否1年分为早期ISR组与晚期SR组。选择同期因冠状动脉原发病变(De novo)置入DES治疗的部分患者作为冠状动脉原发病变组(De novo组)。比较三组患者术后1年的主要不良心血管事件[MACE,包括全因死亡、心肌梗死(MI)和靶病变再次血运重建(TLR)]。结果:早期ISR组入选患者80例,晚期ISR组入选患者124例,De novo组入选患者494例。早期ISR组和晚期ISR组糖尿病患病率明显高于De novo组,差异有统计学意义(36.3%vs.41.1%vs.27.1%,P0.01);早期ISR组不稳定型心绞痛比例明显低于晚期ISR组和De novo组,差异有统计学意义(27.5%vs.63.7%vs.70.6%,P0.01);其余基线资料差异无统计学意义(P0.05)。三组在病变部位、病变类型及病变长度方面比较,差异均无统计学意义(P0.05),而早期ISR组与晚期ISR组直径明显小于De novo组,差异有统计学意义[(2.71±0.36)vs.(2.68±0.41)vs.(3.08±0.54)mm,P0.01)]。早期ISR组MACE发生率明显高于晚期ISR组与De novo组(30%vs.15.3%vs.14.2%,P0.01),其中早期ISR组TLR明显高于晚期ISR组与De novo组,差异有统计学意义(26.3%vs.12.1%vs.10.7%,P0.01),而晚期ISR组与De novo组比较差异无统计学意义(15.3%vs.14.2%,P0.05)。结论:DES治疗ISR患者安全有效,但治疗早期ISR组病变TLR发生率高于晚期ISR组及De novo病变。     

血清内皮细胞特异性分子1、低氧诱导因子1α水平与不稳定型心绞痛PCI术后支架内再狭窄的相关性分析

目的 探讨不稳定型心绞痛(UAP)患者经皮冠状动脉介入治疗(PCI)后血清内皮细胞特异性分子1(ESM-1)、低氧诱导因子1α(HIF-1α)水平与支架内再狭窄(ISR)的相关性。方法 选取2018年3月—2019年4月于本院行PCI术的202例UAP患者为研究对象,根据术后随访1年内是否发生ISR将患者分为两组:ISR组56例和非ISR组146例。采用酶联免疫吸附法检测患者PCI术后24 h血清ESM-1、HIF-1α水平。分析血清ESM-1与HIF-1α水平对ISR的预测价值及影响ISR的因素。结果 ISR组吸烟史比例、血糖、LDLC水平、血清ESM-1、HIF-1α水平高于非ISR组,差异有统计学意义(P＜0.05)。UAP PCI术后ISR患者血清ESM-1水平与HIF-1α水平呈正相关(r＝0.545,P＜0.05)。血清ESM-1、HIF-1α预测UAP患者PCI术后ISR的ROC曲线下面积(AUC)分别为0.913、0.851,特异度分别为87.0%、74.0%,灵敏度分别为82.1%、85.7%;二者联合预测的AUC为0.936,特异度为91.8%,灵敏度为78.6%。ESM-1(≥2.42 μg/L)、吸烟是影响UAP患者PCI术后ISR的独立危险因素(P＜0.05)。结论 UAP患者PCI术后血清ESM-1、HIF-1α水平增高与ISR发生密切相关。     

影响晚期支架内再狭窄患者心脏收缩功能的临床分析

目的对比分析不同射血分数水平的晚期支架内再狭窄(ISR)患者的临床特点,探讨影响晚期ISR患者心脏收缩功能的危险因素。方法入选2010年8月至2017年1月中国人民解放军总医院第一附属医院心内科晚期ISR合并心力衰竭症状的患者共96例,根据左心室射血分数(LVEF)水平分为LVEF下降组9例(LVEF40%)、LVEF中间值组24例(LVEF 40%~49%)和LVEF正常组63例(LVEF≥50%)。比较3组间的临床基线资料和检查资料,行logistic回归分析探讨影响LVEF下降的危险因素。结果 3组间左心房内径、左心室收缩末径和左心室舒张末径比较,差异均有统计学意义(均为P0.01)。3组间陈旧性心肌梗死病史、距离末次介入时间、入院后N末端B型利钠肽原(NT-pro BNP)峰值和高敏C反应蛋白水平比较,差异亦均有统计学意义(均为P0.05)。LVEF下降组ISR患者以ST段抬高型心肌梗死(STEMI)起病的比例显著高于LVEF中间值和正常组(44.4%比12.5%和12.7%,P=0.04)。Logistic回归分析表明,陈旧性心肌梗死病史可作为预测晚期ISR合并心脏收缩功能减退的独立危险因素(OR=2.938,95%CI:1.166~7.407,P=0.022)。结论合并心脏收缩功能减退的晚期ISR患者多以STEMI起病,NT-pro BNP峰值水平更高,既往介入病程更长,病情也更重。陈旧性心肌梗死病史可作为预测晚期ISR患者心脏收缩功能减退的临床因素。     

他汀类药物代谢相关ApoE基因多态性与冠状动脉介入术后再狭窄的相关性研究

目的讨论载脂蛋白E(ApoE)基因多态性对他汀类药物降脂疗效的影响以及与经皮冠状动脉介入术(PCI)后发生支架内再狭窄(ISR)的相关性。方法选取2016年1月至2018年5月期间于辽宁省人民医院心血管内科行PCI术的615例患者为研究对象,根据术后随访1年后行冠状动脉(冠脉)造影复查结果,将患者分为ISR组和非ISR组。比较两组患者的一般临床资料、血液生化指标以及ApoE基因代谢表型携带率;采用二分类Logistic回归模型分析影响ISR发生的危险因素。结果随访1年后,72例发生ISR,543例患者未发生ISR。ISR组患者血清低密度脂蛋白胆固醇(LDL-C)水平以及糖尿病史和高脂血症病史比例高于非ISR组患者(P0.05)。另外,ISR组有13例患者(18.1%)为慢代谢型,慢代谢型患者比例明显高于非ISR组(5.0%)(P0.05)。所有患者服用阿托伐他汀钙12 w后,复查血脂指标。所有患者TG、TC和LDL-C较基线值均有不同程度的下降,而慢代谢型患者TC和LDL-C下降幅度较快代谢型和正常代谢型患者更低(P0.05)。另外,快代谢型患者三酰甘油(TG)、总胆固醇(TC)和LDL-C下降幅度与正常代谢型患者比较未见统计学差异(P0.05)。经二分类Logistic回归分析,快代谢型和正常代谢型是ISR的独立保护因素,且快代谢型的危险性低于正常代谢型。结论 APoE基因多态性与他汀类药物降脂疗效有关,且对PCI术后再狭窄有一定影响。     

冠心病患者PCI前后AT1-AA滴度变化及其与支架内再狭窄的关系

目的探讨冠状动脉粥样硬化性心脏病(冠心病,CHD)患者在经皮冠状动脉介入术(PCI)前和术后血清血管紧张素Ⅱ-1型受体自身抗体(AT1-AA)滴度的变化及其与支架内再狭窄(ISR)的关系。方法选取2018年10月至2020年1月于联勤保障部队第九八九医院心内科行标准PCI(药物洗脱支架)的急性冠脉综合征(ACS)患者145例,PCI前和术后24 h采集血样,采用SA-ELISA法检测血清AT1-AA滴度。根据术后随访冠状动脉(冠脉)造影结果,将患者分为ISR组(ISR≥50%)和非ISR组(ISR50%)。另外检测血清白细胞介素-6(IL-6)、C反应蛋白(CRP)、γ-干扰素(IFN-γ)、血管内皮生长因子(VEGF)、血管生成素1(Ang-1)、Ang-2水平。结果随访期间,43例患者发生ISR,发生率为29.66%。两组PCI术前血清AT1-AA滴度阳性率比较无差异(P0.05)。PCI后,ISR组患者血清AT1-AA滴度阳性率高于PCI术前和非ISR组(P0.05)。经多因素Logistic回归分析,PCI后AT1-AA滴度值是ISR发生的独立预测因素(OR=2.083,95%CI:1.195～3.47,P0.05)。另对于ISR组患者与AT1-AA滴度阴性亚组患者比较,AT1-AA滴度阳性亚组患者血清IL-6、CRP、IFN-γ、VEGF、Ang-2水平更高(P均0.05)。结论 PCI后血清AT1-AA滴度阳性与ISR的发生风险存在独立的相关性,可能与冠脉内皮细胞受损及内膜增生有关,检测血清AT1-AA滴度的分布特征有助于预测PCI术后ISR的发生。     

血清CTRP6、FSTL1联合检测对冠心病患者冠状动脉支架内再狭窄的预测价值

目的 探究血清C1q/肿瘤坏死因子相关蛋白6(CTRP6)、卵泡抑素样蛋白-1(FSTL1)联合检测对冠心病患者行经皮冠脉介入(PCI)术后冠状动脉支架内再狭窄(ISR)的预测价值。方法 选取2020年1月至2021年7月收治的128例冠心病患者作为研究对象,收集患者临床资料。酶联免疫吸附法(ELISA)检测患者血清CTRP6、FSTL1水平。PCI术后随访12个月,根据是否发生ISR分为ISR组(32例)和NISR组(96例),比较两组患者各项指标差异。受试者操作特征(ROC)曲线分析血清CTRP6、FSTL1对冠心病患者PCI术后发生ISR的预测价值。Logistic回归分析冠心病患者PCI术后发生ISR的影响因素。结果 ISR组患者冠状动脉病变长度大于NISR组,植入支架个数多于NISR组(P均<0.05)。ISR组患者血清CTRP6水平显著低于NISR组,FSTL1水平显著高于NISR组(P均<0.05)。随着ISR病变程度的加重,血清CTRP6低表达、FSTL1高表达患者比例逐渐增加,且血清CTRP6低表达、FSTL1高表达的患者病变长度显著大于血清CTRP6高表...     

血浆中基质交感分子1水平与经皮冠状动脉介入术后支架再狭窄的相关性研究

目的探讨血浆中基质交感分子1(STIM1)水平与经皮冠状动脉介入治疗(PCI术后支架内再狭窄(ISR)的相关性。方法选取营口市中心医院2016年6月至2018年6月收治的100例成功接受PCI的冠心病(CHD)患者作为研究对象,术后8个月患者均行冠状动脉造影,对PCI术前和术后STIM1水平进行检测。根据是否发生ISR,将患者分为ISR组和无ISR组(NISR组)。采用Pearson相关分析STIM1水平与PCI术后ISR的相关性,多元线性Logistic回归分析STIM1对PCI患者发生ISR的影响。结果中位随访时间18.2个月,发生ISR患者共36例,NISR组64例。两组患者吸烟史、合并高血压、糖尿病、高血脂、甘油三酯、总胆固醇、高密度脂蛋白胆固醇、植入支架数、支架长度、病变血管数及术前STIM1比较差异无统计学意义(P 0.05)。ISR组和NISR组C反应蛋白(CRP)、术后STIM1、支架直径和术后最小管腔内径比较差异有统计学意义(χ2/t=9.343、8.278、5.991、5.966,P 0.05)。多因素Logistic回归示,术后STIM1、支架直径和术后最小管腔内径是PCI术后ISR的独立危险因素(OR=1.811、2.344、3.515,P 0.05)。STIM1水平与PCI术后ISR呈正相关(r=0.675,P 0.05)。结论 STIM1水平与PCI术后ISR密切关联,是PCI术后ISR的独立危险因素。     

血清补体C1q与经皮冠状动脉药物洗脱支架植入后支架内再狭窄相关性分析

目的目前经皮冠状动脉(冠脉)药物洗脱支架治疗降低了急性冠脉综合征患者的死亡率,然而冠脉支架内再狭窄(ISR)仍是临床中亟待解决的问题。分析支架内再狭窄的相关因素是减少其发生的关键。方法回顾分析于2016年1月至2019年5月于北京安贞医院住院复查冠脉造影的连续病例201例,排除合并感染、支气管哮喘,风湿免疫性疾病、支架植入术后小于12个月的患者(16例),ISR患者(88例,ISR组)以及非ISR患者(97例,非ISR组)纳入研究。比较2组临床特征,血液生化指标差异。受试者工作特征曲线(ROC曲线)及多因素Logistic回归分析血清学指标与支架内再狭窄的相关性。结果ISR组患者血清三酰甘油[(1.55±1.02)vs.(1.23±0.57)mmol/L]、血清小而密低密度脂蛋白[(0.68±0.30)vs.(0.58±0.23)mmol/L]、血清补体C1q[(184.96±37.22)vs.(157.98±20.93)mmol/L]、花生四烯酸介导的血小板聚集率[(11.85±16.79)vs.(6.94±2.53)%]显著高于非ISR组,差异均具有统计学意义。ROC曲线显示血清补体C1q与ISR呈正相关,其诊断ISR的曲线下面积为0.738,P<0.01。以168.95 mg/L为血清补体C1q截点值,其诊断ISR的灵敏度为65.2%,特异度为75%。多因素Logistic回归分析显示,血清补体C1q>168.95 mg/L与ISR呈正相关(OR=4.62,95%CI:2.05~10.40,P<0.01)。结论血清补体C1q水平与经皮冠脉药物洗脱支架内再狭窄密切相关,是支架内再狭窄的诊断因素之一。血清补体C1q是经皮冠脉药物洗脱支架内再狭窄防治的潜在靶点,其在冠脉支架内再狭窄中的作用机制有待进一步研究。     

CYP1A1 , GSTM1 , GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men

AIM: To investigate the role of functional genetic poly-morphisms of metabolic enzymes of tobacco carcinogens in the development of colorectal adenomas. METHODS: The study subjects were 455 patients with colorectal adenomas and 1052 controls with no polyps who underwent total colonoscopy in a preretirement health examination at two Self Defense Forces hospitals. The genetic polymorphisms studied wereCYP1A1*2A (rs 4646903), CYP1A1*2C (rs 1048943), GSTM1 (null or non-null genotype), GSTT1 (null or non-null genotype) and NQO1 C609T (rs 1800566). Genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism or PCR method using genomic DNA extracted from the buffy coat. Cigarette smoking and other life-style factors were ascertained by a self-administered questionnaire. The associations of the polymorphisms with colorectal adenomas were examined by means of OR and 95%CI, which were derived from logistic regression analysis. Statistical adjustment was made for smoking, alcohol use, body mass index and other factors. The gene-gene interaction and effect modification of smoking were evaluated by the likelihood ratio test. RESULTS: None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1 . A borderline significant interaction was observed for the combination of CYP1A1*2C and NQO1 (P = 0.051). The OR associated with CYP1A1*2C was significantly lower than unity among individuals with the NQO1 609CC genotype. The adjusted OR for the combination of the CYP1A1*2C allele and NQO1 609CC genotype was 0.61 (95%CI: 0.42-0.91). Although the interaction was not statistically significant (P = 0.24), the OR for individuals carrying the CYP1A1*2C allele and GSTT1 null genotype decreased significantly compared with those who had neither CYP1A1*2C allele nor GSTT1 null genotype (adjusted OR: 0.69, 95%CI: 0.49-0.97). Smoking did not modify the associations of the individual polymorphisms with colorectal adenomas. There w     

Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands

Amodiaquine (AQ) is a 4‐aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short‐lived quinine‐imine. To complete the genetic variation picture of the main genes involved in AQ metabolism in the Zanzibar population, previously characterised for CYP2C8, we analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately 27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low incidence of fast metabolisers, revealing a relatively safe genetic background in Zanzibar’s population regarding the appearance of adverse effects.     

1-Naphthyl isocyanate and 1-naphthylamine as metabolites of 1-naphthylisothiocyanate

Abstract: The importance of the bioactivation of 1-naphthylisothiocyanate was studied. Forty minutes after 1-naphthylisothiocyanate administration to rats, bile was collected over a 2.5-h period; the liver was then excised and homogenized. 1-naphthylisothiocyanate and its metabolites in bile and liver of rats were identified and quantified using coupled gas chromatography-mass spectrometry. Three main compounds were found in all 1-naphthylisothiocyanate-treated animals. They were identified as 1-naphthyl isocyanate, 1-naphthylamine and the parent compound, 1-naphthylisothiocyanate. When rats were given cycloheximide, which attenuates 1-naphthylisothiocyanate toxicity, 30 min before 1-naphthylisothiocyanate (300 mg/kg), 1-naphthyl isocyanate concentration was significantly lower than in rats receiving only 1-naphthylisothiocyanate. The appearance of 1-naphthylamine was also inhibited by cycloheximide, although not to the same extent as 1-naphthyl isocyanate. On the other hand, phenobarbital, which potentiates 1-naphthylisothiocyanate hepatotoxicity, enhanced 1-naphthyl isocyanate and 1-naphthylamine formation. It is suggested that 1-naphthyl isocyanate, 1-naphthylamine and the highly reactive sulfur released from 1-naphthylisothiocyanate might be involved in the hepatotoxic effect of 1-naphthylisothiocyanate.     

Interleukin-1 and interleukin-1 antagonism.

The polypeptide cytokine interleukin-1 (IL-1) affects nearly every tissue and organ system. IL-1 is the prototype of the pro-inflammatory cytokines in that it induces the expression of a variety of genes and the synthesis of several proteins that, in turn, induce acute and chronic inflammatory changes. IL-1 is also the prototypic "alarm" cytokine in that it brings about increases in a variety of defense mechanisms, particularly immunologic and hematologic responses. Most studies on the biology of IL-1 have been performed in animals, but human subjects have recently been injected with recombinant IL-1 and the results confirm the two fundamental properties of IL-1 as being both a mediator of disease as well as of host defense. However, in either situation, over or continued production of IL-1 leads to debilitation of normal host functions; therefore, reduction of IL-1 synthesis or its effects becomes a target of therapy in many diseases. In this review, the structure, gene expression, synthesis, and secretion of IL-1 are described. In addition, the two IL-1 surface receptors, possible signal transduction mechanisms, various biologic activities, and production of IL-1 during disease states are discussed. Similarities and differences between IL-1, tumor necrosis factor, and IL-6 are presented. Although various agents for reducing the synthesis and/or for antagonizing the effects of IL-1 have been proposed, the recent cloning of a naturally occurring IL-1 receptor antagonist (IL-1ra) has opened new experimental and clinical approaches. The ability of this IL-1ra to block the triggering of IL-1 receptors in animals without agonist effects has reduced the severity of diseases such as hemodynamic shock, lethal sepsis, inflammatory bowel disease, experimental arthritis, and the spontaneous proliferation of human leukemic cells.     

甲型H1N1与季节性H1N1流感病毒血凝素基因比较分析

目的分析泰安市2008～2009年度季节性流感与2009年度甲型H1N1流感病原学检测结果 ,比较季节性H1N1与甲型H1N1血凝素基因变异情况。方法选择国家级流感监测哨点医院以及暴发疫情的疫点,采集流感样病例的鼻咽拭子标本,通过RealtimePCR进行病毒检测,用MDCK细胞进行病毒分离,通过RT-PCR扩增血凝素HA1片段的基因并测序,利用生物信息学进行序列分析。结果 2008～2009年共检测鼻咽拭子标本283份,分离出流感病毒33株,分离阳性率为11.67%,其中季节性H1N1亚型31株。2009年5月1日～12月31日,检测鼻咽拭子标本996份,流感核酸检测阳性417份,阳性率为41.86%,其中甲型H1N1337份,季节性H1N1亚型1份。6株季节性H1N1病毒均在多个氨基酸位点上发生变异,与疫苗株A/Brisbane/59/2007(H1N1)比较,有11个位点发生了突变,其中5个位点位于抗原决定簇上;测序成功的6株甲型H1N1病毒在多个氨基酸位点发生变异,与疫苗株A/California/07/2009(H1N1)比较,有6个位点发生突变,其中1个位点位于抗原决定簇的B区。结论 2008～2009年度季节性H1N1为优势株,甲流暴发后,甲型H1N1成为绝对优势毒株。季节性H1N1分离株有多处氨基酸替换,抗原决定簇B区变异频繁;甲型H1N1病毒分离株的基因有变异,但关键位点第222位仍为D(天冬氨酸),与疫苗株相比抗原决定簇的关键位点变化不大。     

Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis

Cooperative activation of Meis1 and Hoxa9 perturbs myeloid differentiation and eventually leads myeloid progenitors to leukemia, yet it remains to be clarified what kinds of subsequent molecular processes are required for development of overt leukemia. To understand the molecular pathway in Hoxa9/Meis1-induced leukemogenesis, retroviral insertional mutagenesis was applied using retrovirus-mediated gene transfer. The mice that received Hoxa9/Meis1-transduced bone marrow cells developed acute myeloid leukemia (AML), and Trib1, Evi1, Ahi1, Raralpha, Pitpnb, and AK039950 were identified as candidate cooperative genes located near common retroviral integration sites. Trib1 and Evi1 were up-regulated due to retroviral insertions, and coexpression of these genes significantly accelerated the onset of Hoxa9/Meis1-induced AML, suggesting that Trib1 and Evi1 are the key collaborators. Furthermore, Trib1 by itself is a novel myeloid oncogene, enhancing phosphorylation of ERK, resulting in inhibition of apoptosis. These results demonstrate the importance of specific oncogene interaction in myeloid leukemogenesis.     

GSTT1, GSTM1 and GSTP1 polymorphisms and susceptibility to juvenile idiopathic arthritis

OBJECTIVE: In this study we have analyzed GSTM1, GSTT1 and GSTP1 polymorphisms in patients with juvenile idiopathic arthritis (JIA), to investigate a possible role of these genes as genetic components of the disease. METHODS: A total of 103 individuals (49 oligoarticular, 41 polyarticular and 13 systemic) were analyzed for the three polymorphisms, using a PCR/RFLP methodology. RESULTS: We have observed significantly increased frequencies of individuals with GSTT1 null genotype in JIA patients comparing to controls (37% x 21%; p=0.0183). There was a 2-fold increased risk (OR 2.2, 95% CI 1.2-4.1) associating the disease with the GSTT1 null genotype. Considering the subgroups (oligoarticular, polyarticular and systemic), the results indicated an association between polyarticular and systemic patients and the GSTT1 null genotype. There was a 2-fold increased risk for polyarticular patients (OR 2.4, 95%, CI 1.1-5.4), and a 4-fold increased risk for systemic patients (OR 4.4, 95%, 1.3-14.5). CONCLUSION: The GSTT1 null genotype seems to be involved in polyarticular and systemic JIA.     

Glutathione S-transferase M1, T1, and P1 genotypes and rheumatoid arthritis

OBJECTIVE: To determine the effects of genetic polymorphisms of glutathione S-transferase (GST) M1, GSTT1, and GSTP on risk and severity of rheumatoid arthritis (RA) in a Korean population. METHODS: A total of 258 patients with RA and 400 disease-free controls were enrolled. GST genotypes were determined by RFLP-PCR. HLA-DRB 1 typing and further subtyping of all alleles was performed using sequence-specific oligonucleotide probe hybridization after PCR. Severity of RA among cases was assessed by Steinbrocker anatomical stage. Risk was assessed by calculating the age and sex adjusted odds ratio (OR) and 95% confidence intervals (CI). RESULTS: The OR for risk of RA with the GSTM1-null genotype was 1.40 (95% CI 1.02- 1.92, p = 0.04), and 1.86 (95% CI 1.12- 3.09, p = 0.005) among individuals without the shared epitope (SE). Among patients with RA, the OR for risk of severe RA for the GSTM1-null genotype was 2.45 (95% CI 1.04- 5.77, p = 0.02). No association was observed between the GSTT1 or GSTP1 genotypes and either risk or severity of RA. CONCLUSION: These results suggest that the deletion polymorphism of GSTM1 is associated with increased susceptibility for RA, particularly among individuals who are not carriers of the HLA-DRB 1 SE.