[目的]研究CYP19A1基因的rs4646和rs10046位点多态性与晚期乳腺癌阿那曲唑治疗疗效的相关性。[方法]本研究共纳入272例激素受体阳性晚期乳腺癌患者,接受阿那曲唑治疗后抽取患者外周静脉血,提取DNA,多重PCR获取目的基因片段后,采用直接...[目的]研究CYP19A1基因的rs4646和rs10046位点多态性与晚期乳腺癌阿那曲唑治疗疗效的相关性。[方法]本研究共纳入272例激素受体阳性晚期乳腺癌患者,接受阿那曲唑治疗后抽取患者外周静脉血,提取DNA,多重PCR获取目的基因片段后,采用直接测序法分析CYP19A1基因多态性。对比等位基因分布频率在突变型和野生型两组患者中的差异。[结果]被检测的rs4646和rs10046符合Hardy-Weinberg平衡检验;比较rs4646突变型和野生型两组阿那曲唑疗效,32例完全缓解的患者中24例是rs4646突变型,76例疾病进展者中有60例是rs4646野生型,P<0.005,经过Bonferroni矫正P值仍有统计学意义。与rs4646野生型相比,携带rs4646突变型患者的中位生存期(median survival time,MST)显著延长(Log-rank检验P=0.007)。携带rs4646突变型患者的疾病进展时间(time to progression,TTP)显著延长(Log-rank检验P=0.049)。[结论]rs4646多态性位点可能会成为预测晚期乳腺癌阿那曲唑治疗疗效和预后的预测因子。展开更多
Temperature-dependent sex determination（TSD） is a type of environmental sex determination in which the sex of the embryos depends on the ambient temperature; however,the molecular mechanisms governing this process r...Temperature-dependent sex determination（TSD） is a type of environmental sex determination in which the sex of the embryos depends on the ambient temperature; however,the molecular mechanisms governing this process remain unknown.Aromatase,encoded by the cyp19a1 gene,which converts androgens into estrogens in animals,was considered to be the key gene for TSD.In this study,the 5＇-flanking region of the cyp19a1 gene in Reeves＇ turtle（Mauremys reevesii） was cloned,and the promoter region was identified using the luciferase reporter assay.Then the eggs of Reeves＇ turtle were incubated at different temperatures（26°C： male-biased temperature; 29°C： non-sex-biased temperature and 32°C： female-biased temperature）.During the thermosensitive period,the adrenal kidney gonad complexes（AKG） were sampled.DNA methylation analysis of the AKG samples showed that the promoter region of the cyp19a1 gene was significantly de-methylated in the female-biased temperature regime（P＆lt;0.01）.Quantitative analysis of the cyp19a1 gene and estrogen by q PCR and Elisa assay showed that the expression level of the cyp19a1 gene and estrogen content were both upregulated significantly at the female-biased temperature（P＆lt;0.01）.These results indicated that the de-methylation response of the cyp19a1 gene to incubation temperature,especially at the female-biased temperature,could lead to temperature-specific expression of aromatase and increased estrogen levels,which may further determine gonadal development in Reeves＇ turtle.These findings provide insights into the genetic mechanisms underlying TSD.展开更多
文摘[目的]研究CYP19A1基因的rs4646和rs10046位点多态性与晚期乳腺癌阿那曲唑治疗疗效的相关性。[方法]本研究共纳入272例激素受体阳性晚期乳腺癌患者,接受阿那曲唑治疗后抽取患者外周静脉血,提取DNA,多重PCR获取目的基因片段后,采用直接测序法分析CYP19A1基因多态性。对比等位基因分布频率在突变型和野生型两组患者中的差异。[结果]被检测的rs4646和rs10046符合Hardy-Weinberg平衡检验;比较rs4646突变型和野生型两组阿那曲唑疗效,32例完全缓解的患者中24例是rs4646突变型,76例疾病进展者中有60例是rs4646野生型,P<0.005,经过Bonferroni矫正P值仍有统计学意义。与rs4646野生型相比,携带rs4646突变型患者的中位生存期(median survival time,MST)显著延长(Log-rank检验P=0.007)。携带rs4646突变型患者的疾病进展时间(time to progression,TTP)显著延长(Log-rank检验P=0.049)。[结论]rs4646多态性位点可能会成为预测晚期乳腺癌阿那曲唑治疗疗效和预后的预测因子。
基金supported financially by the National Natural Science Foundation of China(Nos.31401053 and 31471966)Guangdong Provincial Natural Science Foundation of China(No.2015A030313903)+1 种基金GDAS Special Project of Science and Technology Development(2017GDASCX-0107)the Funds for Environment Construction and Capacity Building of GDAS’Research Platform(2016GDASPT-0107)
文摘Temperature-dependent sex determination（TSD） is a type of environmental sex determination in which the sex of the embryos depends on the ambient temperature; however,the molecular mechanisms governing this process remain unknown.Aromatase,encoded by the cyp19a1 gene,which converts androgens into estrogens in animals,was considered to be the key gene for TSD.In this study,the 5＇-flanking region of the cyp19a1 gene in Reeves＇ turtle（Mauremys reevesii） was cloned,and the promoter region was identified using the luciferase reporter assay.Then the eggs of Reeves＇ turtle were incubated at different temperatures（26°C： male-biased temperature; 29°C： non-sex-biased temperature and 32°C： female-biased temperature）.During the thermosensitive period,the adrenal kidney gonad complexes（AKG） were sampled.DNA methylation analysis of the AKG samples showed that the promoter region of the cyp19a1 gene was significantly de-methylated in the female-biased temperature regime（P＆lt;0.01）.Quantitative analysis of the cyp19a1 gene and estrogen by q PCR and Elisa assay showed that the expression level of the cyp19a1 gene and estrogen content were both upregulated significantly at the female-biased temperature（P＆lt;0.01）.These results indicated that the de-methylation response of the cyp19a1 gene to incubation temperature,especially at the female-biased temperature,could lead to temperature-specific expression of aromatase and increased estrogen levels,which may further determine gonadal development in Reeves＇ turtle.These findings provide insights into the genetic mechanisms underlying TSD.
