Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival

ObjectivePrognostic biomarkers that distinguish between patients with good or poor outcome can be used to guide decisions of whom to treat and how aggressively. In this sense, several groups have proposed genetic polymorphisms as potential susceptibility and prognostic biomarkers; however, their validity has not been proven. Thus, the main goal of the present work was to investigate the potential role of single and combined CYP1A1, GSTM1, and GSTT1 genotypes as modifiers of cancer survival in Chilean patients with prostate cancer.Methods and materialsA total of 260 histologically confirmed patients were recruited from a voluntary screening, and genomic DNA was obtained from their blood samples for genotyping analyses to detect the CYP1A1*2A polymorphism and GSTM1 and GSTT1 deletions. The progression of illness and mortality were estimated with a median follow-up of 8.82 years. Adjusted estimated genotype risks were evaluated by hazard ratio and 95% CI using the Cox proportional model. In addition, the Kaplan-Meier survival method and log-rank test were used to evaluate patient survival with regard to genotype.ResultsThe 9-year overall and specific survival rates were 67.6% and 36.6% in the GSTT1null group, 67.6% and 58.7% in the GSTM1non-null group, 69.0% and 51.6% in the *1A/*2A group, 63.9% and 61.5% in the *2A/*2A group vs. 76.2% and 62.3% in the GSTT1non-null group, 82.3% and 50% in the GSTM1null group, and 83.7% and 56.3% in the *1A/*1A group, respectively. The hazard ratios and the Kaplan-Meier curve results demonstrate that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes are significantly associated with mortality. Our study has two main limitations: a relatively small sample size and a low global mortality percentage (25.4%); thus, we need to continue the follow-up to confirm these findings.ConclusionsOur results suggest that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes may be good prognosis markers, particularly in patients with high-risk tumors.     

NRAMP1基因3′UTR多态现象与汉族结核病易感性的研究

目的 研究人类自然抵抗相关巨噬细胞蛋白(NRAMP1)基因3’UTRR多态现象与汉族结核病易感性的关系。方法 选取汉族活动性结核病患147例，正常对照145人，用聚合酶链反应-限制性片断长度多态性(PCR—RFLP)的方法对NRAMP1基因3’UTR进行基因分型，根据基因型对样本分组，经统计学处理，研究3’UTR多态现象与结核病易感性的关系。结果 在活动性结核病患中3’UTR TGTG／TGTG基因型95例(64．6％)，TGTG／TTTG缺失基因型50例(34．0％)，TGTG缺失／TGTG缺失基因型2例(1．4％)；正常对照TGTG／TGTG基因型则为115例(79．3％)，TGTG／TGTG缺失基因型29例(20．0％)，TGTG缺失／TGTG缺失基因型1例(0．7％)。正常对照组TGTG／TGTG基因型明显高于结核病患(x^2＝7．79；P＜0．01)。研究发现TGTG的等位基因频率为0．85，TGTG缺失的等位基因频率为0．15。结论 NRAMP1基因3’UTR多态现象与结核病易感性相关，汉族3’UTR TGTG缺失等位基因频率明显高于白种人，可部分解释汉族比白种人更易患结核病。     

Association of rs1285933 single nucleotide polymorphism in CLEC5A gene with dengue severity and its functional effects

Outbreaks of the Zika, dengue, and chikungunya viruses, especially in the Americas, pose a global threat due to their rapid spread and difficulty controlling the vector. Extreme phenotypes are often observed, from asymptomatic to severe clinical manifestations, which are well-studied in dengue. Host variations are also important contributors to disease outcomes, and many case-control studies have associated single nucleotide polymorphisms (SNPs) with severe dengue. Here, we found that the TC genotype and T-carriers for SNP rs1285933 in the C-type lectin superfamily member 5 (CLEC5A) gene was associated with severe dengue in a Northern Brazilian population (OR = 2.75 and p-value = 0.01, OR = 2.11 and p-value = 0.04, respectively). We also tested the functional effect of the CLEC5A protein and found that it is upregulated on the surface of human monocytes after in vitro dengue infection. CLEC5A was correlated with viral load inside the monocytes (Spearman r = 0.55, p = 0.008) and TNF production in culture supernatants (Spearman r = 0.72, p = 0.03). Analysis of mRNA in blood samples from DENV4-infected patients exhibiting mild symptoms showed that CLEC5A mRNA expression is correlated with TNF (r = 0.67, p = 0.0001) and other immune mediators. Monocytes from rs1285933 TT/TC individuals showed lower CLEC5A expression compared to CC genotypes. However, in these cells, CLEC5A was not correlated with TNF production. In summary, we confirmed that CLEC5A is genetically associated with dengue severity outcome, playing a central role during the immune response triggered by a dengue viral infection, and rs1285933 is a relevant SNP that is able to regulate signaling pathways after interactions between the dengue virus and CLEC5A receptors.     

荧光杂交探针实时聚合酶链式反应快速检测甘露聚糖结合凝集素启动子区基因变异方法的建立

目的建立用荧光杂交探针实时聚合酶链式反应（Real-timePCR）检测人甘露聚糖结合凝集素（MBL）启动子区基因变异新型的基因分型法——Tm基因分型法。方法收集30例健康献血员外周抗凝全血,提取基因组DNA。通过LightCycler实时PCR仪描绘扩增的目标DNA片段的熔解曲线,根据熔解温度（Tm）峰值判定待测标本的基因变异类型。最后,用基因测序法检测PCR产物来验证Tm基因分型法的准确性。结果建立了新型的Tm基因分型法,且测定PCR产物的时间仅180min,检测结果与测序法完全吻合。结论Tm基因分型法检测人MBL启动子区基因变异快速、准确,重复性好,具有广泛的临床应用前景。     

PGC-1基因Ser74Leu、IVS2+52C＞A多态与2型糖尿病的相关性研究

目的 探索中国延边朝鲜族、汉族人群的PGC-1基因Ser74Leu、IVS2 52C＞A多态与2型糖尿病(T2DM)的相关性.方法 采用聚合酶链反应-单链构象多态性技术(PCR-SSCP)确定PGC-1基因的第2外显子及第2内含子的Ser74Leu、IVS2 52C＞A多态位点的基因型,比较等位基因频率及基因型频率在民族之间差异.结果 1. 朝鲜族和汉族的T2DM、NGT组间的PGC-1基因Ser74Leu(C＞A)、IVS2 52(C＞A)两个等位基因三种单体型的频率分布比较未见差异(P=0.178, P=0.671);2. T2DM组中,朝鲜族表型为CC-CA/CC-AA的腰臀比(WHR)水平较表型为CC-CC的高(P=0.030),汉族表型为CC-CA/CC-AA的空腹血糖(FPG)水平高于表型为CC-CC(P=0.005).结论 PGC-1基因可能是中国延边朝鲜族和汉族2型糖尿病的发病的易感基因.     

Matrix metalloproteinase-9-1562C〉T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer

AIM: To explore the role of the matrix metalloproteinase-9 (MMP-9) polymorphism in colorectal cancer (CRC) in a northeast Chinese population. METHODS: Genotyping of MMP-9 -1562C>T and 279R>Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The distribution of MMP-9 -1562C>T and 279 R>Q genotype was not significantly associated with the risk of CRC. However, the risk of llymph node metastasis of CRC was increased in patients with the -1562T allele (OR = 2.601; 95% CI = 1.160-5.835; P = 0.022). The frequency of MMP-9 279RR RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old (OR = 0.102; 95% CI = 0.013-0.812; P = 0.012). CONCLUSION: Our results indicated that the MMP-9-1562C>T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer.     

KIF6基因rs20455多态性与中国北方汉族人冠心病及血脂水平的关联研究

目的分析KIF6基因rs20455多态性与中国北方汉族人群冠心病及血脂水平的关系。方法收集164例冠心病(CHD)患者及152例健康人的外周血标本;应用聚合酶链反应-限制性片段长度多态性技术检测KIF6 rs20455多态性;研究基因多态性对血糖、血脂水平的可能影响。结果中国北方汉族人KIF6基因rs20455多态性位点TT、TC、CC基因型频率分别为0.291,0.491与0.218;T等位基因,C等位基因频率分别为0.536与0.464。基因型和等位基因频率在组间分布差异均无统计学意义(P>0.05)。本研究对象rs20455多态性基因型和等位基因频率分布与高加索,非裔美洲人群有统计学差异(P<0.001)。rs20455基因多态性与血糖、血脂水平、性别、年龄、高血压病史无显著性关联。Logistic回归显示,年龄、TG、HbAlc是本组研究对象发生冠心病的主要危险因素(OR分别为1.178、26.18、17.415,P<0.05)。C等位基因不是发生冠心病的独立危险因素。结论未发现KIF6基因rs20455多态性与本研究人群的冠心病发生及血脂水平存在明显关联性。     

非家族性心房颤动与血管紧张素基因I/D多态性关系的研究

目的探讨肾素血管紧张素系统(RAS)中的血管紧张素转换酶(angiotensin 1-converting enzyme,ACE)基因多态性与黑龙江地区人群非家族性房颤的发生关系。方法选取ACE基因I/D位点进行分析。采用病例-对照实验设计,研究对象共400例,均来自黑龙江省,包括非家族性房颤者200例和对照组200例。本研究采用聚合酶链反应(polymerase chain reaction,PCR)技术。结果ACEI/D位点与房颤发生显著相关,疾病组中的ACE-D等位频率显著高于对照组。结论RAS基因可能不仅是高血压病的候选基因,也有可能是非家族性房颤的候选基因。     

基因多态性与肾移植患者他克莫司个体化治疗研究进展

目的:他克莫司(tacrolimus,FK506)是防治肾移植术后排斥反应的常用药,其狭窄的治疗窗和药动学及药效学方面显著的个体差异一直困扰着临床。现有研究表明,CYP3A4、CYP3A5、MDR1单倍型以及IL-10、PXR基因多态性可能对FK506的药动学和药效学产生不同影响,进一步深入研究基因多态性对临床实施肾移植患者个体化治疗具有十分重要的意义。方法:对国内外近期文献进行分析。结果与结论:进一步系统查明CYP3A4、CYP3A5、MDR1单倍型以及IL-10、PXR基因多态性对指导肾移植患者FK506个体化用药具有十分重要的意义。     

国人载脂蛋白E基因多态性与冠心病发病之间的相关性

目的 探讨载脂蛋白E基因112bp与158bp位点多态性与血脂水平及冠心病发生之间的关系。方法采用生物化学法分别测量经冠状动脉造影证实的89例冠心病患者及43例正常人空腹血脂水平，应用聚合酶链反应限制片长多态性分析方法对载脂蛋白E基因DNA244bp的5’末端片段进行限制性片段长度多态性分析。结果冠心病组甘油三酯、总胆固醇、低密度脂蛋白、载脂蛋白B及脂蛋白（a）水平均高于对照组（P〈0．05），而载脂蛋白A1水平则低于对照组（P〈0、05）；冠心病组载脂蛋白Eε2基因型频率明显为低（P〈0．001）。结论载脂蛋白E基因多态性特征会明显影响人群中个体的血浆脂质水平，从而增加人群中个体发生冠心病的危险。