TP53基因rs1042522单核苷酸多态性与男性不育相关性研究

目的:探讨肿瘤蛋白p53(TP53)基因rs1042522位点单核苷酸多态性与男性不育的关系。方法:采用病例-对照研究,收集南京地区特发性男性不育患者380例(病例组),有生育史的健康男性398例(对照组);并将病例组分为无精子症组(n=140)和少精子症组(n=240)。用Sequence Mass Array技术检测TP53基因rs1042522位点的基因型,通过Logistic回归分析该位点多态性与男性不育的相关性。结果:病例组与对照组前向运动精子百分率[(10.38±5.57)%vs(42.55±9.57)%]、精子浓度[(13.13±24.96)×106/ml vs(77.34±49.24)×106/ml]、T[(14.07±5.36)nmol/L vs(11.89±4.50)nmol/L]、FSH[(16.80±18.20)U/L vs(4.55±7.17)U/L]存在显著性差异(P<0.05)。经Logistic回归分析,未发现各基因型与男性不育有统计学意义的相关性,亚组分析也未发现相关性。结论:TP53基因rs1042522位点的单核苷酸多态性与男性不育无显著相关性。

P53 rs1042522 and CD95 rs1800682 genetic variations in HCV-4a response to antiviral therapy

Current estimates indicate that the hepatitis C(HCV)is the leading cause of mortality around the world,with infection rates steadily increasing in Egypt.The dual therapy for this silent epidemic with pegylated-interferon-a2b/ribavirin has markedly improved the success rates in genotype-4 patients.It was reported that apoptosis plays a vital mechanistic role in limiting viral replication.P53,a key regulator of apoptosis,induces CD95 gene expression and subsequently initiates apoptotic cascade to be activated.The current study examined the impact of P53 rs1042522 and CD95 rs1800682 polymorphisms on the treatment response.Three groups of 240 volunteers were enrolled in this study;86 in sustained virological responders group,74 in non-responders group,and 80 in control group.All patients had HCV genotype-4a and were interferon treatment naı¨ve.Quantizations of HCV-RNA by qRT-PCR and histological scores were performed for all patients.In addition,genotyping of HCV-RNA,P53 rs1042522 Arg/Pro and CD95 rs1800682 A/G polymorphisms were investigated in all subjects.It was resulted that P53 Pro/Pro homozygous genotype has high significant increase,while CD95 A/A homozygous genotype has high significant decrease when comparing non-responders with responders.Finally,it was concluded that Pro variant of P53 rs1042522 may be used as a genetic predictor for non-responsiveness,while A/A variant of CD95 rs1800682 may be used as a sensitive biomarker for responsiveness to antiviral therapy of HCV genotype-4a infection.In addition,low prolactin,high total testosterone,and high GH levels may provide promising biomarkers for early prediction of the response when associated with these genetic polymorphisms.

p53 Arg72pro基因多态性与宫颈癌放化疗敏感性的相关性

目的探讨p53 Arg72pro基因多态性与宫颈癌放化疗敏感性的关系。方法收集ⅡB~ⅣA期接受同期放化疗治疗的宫颈癌患者,采用PCR荧光探针法对研究对象进行p53 Arg72pro(rs1042522)位点基因分型检测。疗效评价采用实体瘤RECIST 1.1标准。将基因型、年龄、分期、分化程度、肿瘤大小、淋巴结转移等因素纳入logistic回归模型,分析宫颈癌同步放化疗敏感性的影响因素,并评价logistic模型的预测效果。结果纳入符合条件的105例患者,中位随访时间为6月。p53 Arg72pro基因分型符合HardyWeinberg平衡,多因素logistic回归分析显示C/G基因型可增加肿瘤放化疗敏感性。而高龄、低分化、淋巴结转移、肿瘤> 4 cm等临床因素均显著降低放化疗敏感性(P <0.05)。结论 P53 Arg 72pro基因多态性是预测宫颈癌同期放化疗敏感性的独立影响因素,其中C/G和G/G基因型可增加肿瘤放化疗敏感性。