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Association between Maternal Drug Use and Cytochrome P450 Genetic Polymorphisms and the Risk of Congenital Heart Defects in Offspring 被引量:1
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作者 QIN Jia Bi LUO Liu +8 位作者 SUN Meng Ting HUANG Peng WANG Ting Ting ZHANG Sen Mao LI Jin Qi LI Yi Huan CHEN Le Tao DIAO Jing Yi ZHU Ping 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2022年第1期45-57,共13页
Objective This study aimed to assess the associations between maternal drug use,cytochrome P450(CYP450)genetic polymorphisms,and their interactions with the risk of congenital heart defects(CHDs)in offspring.Methods A... Objective This study aimed to assess the associations between maternal drug use,cytochrome P450(CYP450)genetic polymorphisms,and their interactions with the risk of congenital heart defects(CHDs)in offspring.Methods A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.Results After adjusting for potential confounding factors,the results show that mothers who used ovulatory drugs(adjusted odds ratio[a OR]=2.12;95% confidence interval[CI]:1.08-4.16),antidepressants(a OR=2.56;95%CI:1.36-4.82),antiabortifacients(a OR=1.55;95%CI:1.00-2.40),or traditional Chinese drugs(a OR=1.97;95%CI:1.26-3.09)during pregnancy were at a significantly higher risk of CHDs in offspring.Maternal CYP450 genetic polymorphisms at rs1065852(A/T vs.A/A:OR=1.53,95%CI:1.10-2.14;T/T vs.A/A:OR=1.57,95%CI:1.07-2.31)and rs16947(G/G vs.C/C:OR=3.41,95%CI:1.82-6.39)were also significantly associated with the risk of CHDs in offspring.Additionally,significant interactions were observed between the CYP450 genetic variants and drug use on the development of CHDs.Conclusions In those of Chinese descent,ovulatory drugs,antidepressants,antiabortifacients,and traditional Chinese medicines may be associated with the risk of CHDs in offspring.Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development. 展开更多
关键词 congenital heart defect Maternal drug use cytochrome p450 genes case-control study
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Relation of cytochrome P450 2C19 gene 681G>A single nucleotide polynmrphism to clopidogrel resistance after PCI in Chinese
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作者 LIANG Zhen-yang,HAN Ya-ling,ZHANG Xiao-lin,YAN Cheng-hui (Department of Cardiology,Cardiovascular Institute of PLA, Shenyang Northern Hospital.Shenyang 110031,China) 《岭南心血管病杂志》 2011年第S1期155-155,共1页
Objectives Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450(CYP) isoenzymes to inhibit platelet aggregation.Individualvariability of platelet inhibition by clopidogr... Objectives Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450(CYP) isoenzymes to inhibit platelet aggregation.Individualvariability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness.In this study,we sought to determine the association between the single nucleotide polymorphism of CYP 2C19 681G】A and the occurrence of clopidogrel resistance(CR) in Chinese.Methods The study enrolled 614 hospitalized patients who underwentsuccessful percutaneouscoronary intervention with drug-eluting stents were received the treatmentwith dual antiplatelet regimen(aspirin plus clopidogrel).All patients received loading doses of 600 mg clopidogrel and 300 mg aspirin.20μmol/L ADP-induced platelet aggregation ratio(PAR ) was assessed 24 h after clopi- dogrel administration.The maximum residual PAR≥70%was defined as CR.Genomic DNA was extracted from whole blood samples according to standard protocols,the single nucleotide polymorphism of the CYP2C19 681G】A was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all the patients.Results CR was found in 126 patients(20.5%).There was CYP2C19 681G】A polymorphism in the study population.The frequencies of the three kinds of genotypes(GG,GA,A A) in CR group and non-CR (NCR)group were 32.5%,47.6%,19.8%and 48.0%, 45.0%,7.0%,respectively.The frequency of AA genotype was significantly higher in NCR group than that in CR group (OR =3.03,95%CI:1.889~5.784,P=0.003).The A allele carriers were more likely to develop clopidogrel resistance compared with that of G allele carriers(OR=1.85,95%CI: 1.392~2.459,P=0.002).Conclusions CYP2C19 681G/A polymorphism is associated with the risk of CR,and the A allele carriers may be a possible genetic susceptibility factor for patients with CR. 展开更多
关键词 pcI Relation of cytochrome p450 2c19 gene 681G>A single nucleotide polynmrphism to clopidogrel resistance after pcI in chinese gene
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Cytochrome P450 Directed Prodrug Activation Therapy in Research of Cancer Enzymology
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作者 周江泉 汤致强 《Journal of Chinese Pharmaceutical Sciences》 CAS 2005年第1期1-9,共9页
Cancer enzymology is a promising filiation of bio-medical sciences. In thepast decades, enzymes, such as GST(glutathione S-transferase) , PKC(protein kinase C) , Topo(DNAtopoisomerases), TK(tyrosine kinase), CD (bacte... Cancer enzymology is a promising filiation of bio-medical sciences. In thepast decades, enzymes, such as GST(glutathione S-transferase) , PKC(protein kinase C) , Topo(DNAtopoisomerases), TK(tyrosine kinase), CD (bacterial cytosine deaminase), CPG2(carboxypeptidase G2) ,and PNP (purine nucleoside phosphorylase), have been known to bear close relations to cancer. Theirspecific expression and influence on the process of tumor initiation, promotion and progressionattract scientists to apply them as a biochemical marker of certain malignant tumor, a predictor ofresponse in cancer chemotherapy; to apply them to drug design, tumor prevention and as adjuvant toradiotherapy or surgery. 展开更多
关键词 cytochrome p450 cancer enzymology gene directed enzyme prodrug therapy(GDEpT) structure-function relationship selective delivery
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Cytochrome P450 2E1 RsaI/PstI and DraI Polymorphisms Are Risk Factors for Lung Cancer in Mongolian and Han Population in Inner Mongolia 被引量:3
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作者 Xiu-lan Su Ba Bin +1 位作者 Hong-wei Cui Mei-rong Ran 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2011年第2期107-111,共5页
Objective: To explore the relationship between cytochrome P450 2E1 (CYP2E1) RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods: CYP2E... Objective: To explore the relationship between cytochrome P450 2E1 (CYP2E1) RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods: CYP2E1 RsaI/PstI and DraI polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals. The distribution of genotype and allele frequencies of CYP2E1 RsaI/PstI and DraI polymorphisms were studied. Results: The risk of lung cancer was increased in individuals with CYP2E1 (cl/cl) and CYP2E1 (DD) with OR values of 2.431 (95%CI=1.082-5.460) and 2.778 (95%CI=1.358-5.683) respectively (P0.05). When CYP2E1 RsaI/PstI and DraI polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 (cl/c2+c2/c2 and DD+CC) with OR values of 0.233 (95%CI=0.088-0.615, P0.05). In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 (c1/c1) and CYP2E1 (DD) than in the individuals with c2 and C allele (P0.05, OR=2.643 and 4.308 respectively). There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion: CYP2E1 (c1/c1) and CYP2E1 (DD) are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 (c2﹢C) co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 (c1/c1) and CYP2E1 (DD) on the occurrence of lung cancer. 展开更多
关键词 cytochrome p450 2E1 gene polymorphism Lung cancer Susceptivity
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Response of Cytochrome P450 Expression to Maize Volatiles in Helicoverpa armigera (Hner) 被引量:2
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作者 WU Shao-ying SHI Xue-yan +1 位作者 WANG Yi GAO Xi-wu 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2013年第4期646-652,共7页
The 7-ethoxycoumarin O-deethylase (ECOD) activities of cytochrome P450s and differential expression of six cytochrome P450 genes induced by the volatiles from both damaged and undamaged maize plants were investigate... The 7-ethoxycoumarin O-deethylase (ECOD) activities of cytochrome P450s and differential expression of six cytochrome P450 genes induced by the volatiles from both damaged and undamaged maize plants were investigated in the cotton bollworm, Helicoverpa armigera (Hiabner). The ECOD activity changed with time of exposure to maize volatiles. At 36 h after cotton bollworm larvae exposure to maize volatiles, the ECOD activities in cotton bollworm damaged and artificially damaged groups were 2.36 and 4.53 times higher than the control group respectively. The relative expression levels of CYP4S1, CYP6B2 and CYP6B7 in the cotton bollworm were significantly increased in artificially damaged plant group, which was 2.93, 5.09 and 10.66 times higher than that in the control group, respectively. The expression levels of CYP6B2, CYP6B6, CYP9A12, and CYP9A14 were much lower in the larvae exposure to volatiles from both healthy and pest damaged maize seedlings than in the control group at 12 h after larvae exposure to maize volatiles. For the cotton bollworm damaged maize group, the expression of CYP4S1 and CYP9A14 increased. 展开更多
关键词 7-ethoxycoumarin O-deethylase cytochrome p450 gene maize volatile Helicoverpa armigera
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细胞色素P450 CYP2E1酶构型特征及其表达调控机制的研究进展 被引量:26
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作者 刘晨晖 乐江 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2010年第2期155-160,共6页
细胞色素P450CYP2E1酶参与代谢活化及失活多种前毒物、前致癌物和少数药物。在细胞色素P450超家族中,CYP2E1具有易介导自由基生成引发氧化应激反应的特征。CYP2E1表达水平可能是机体对环境和工业毒物或致癌物敏感程度的重要因素。研究表... 细胞色素P450CYP2E1酶参与代谢活化及失活多种前毒物、前致癌物和少数药物。在细胞色素P450超家族中,CYP2E1具有易介导自由基生成引发氧化应激反应的特征。CYP2E1表达水平可能是机体对环境和工业毒物或致癌物敏感程度的重要因素。研究表明,CYP2E1可被多种内、外源性物质所调控,并且CYP2E1的药理和毒理学功能与其以蛋白构型为基础的代谢行为密切相关。本文综述了CYP2E1基因多态性、酶构型特征与其代谢活性间的关系,并分析了其区别于其他细胞色素P450亚型的表达调控机制。 展开更多
关键词 细胞色素p450 cYp2E1 蛋白质结构 二级 基因表达调控 自由基
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人CYP450 2E1异源性表达模型的建立及底物的表达诱导作用 被引量:2
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作者 王水良 贺智敏 +2 位作者 朱建华 侯德富 陈主初 《中国病理生理杂志》 CAS CSCD 北大核心 2004年第2期166-169,共4页
目的 :探讨化学致癌物二亚硝基哌嗪 (DNP)对人CYP2E1异源表达的诱导作用。方法 :脂质体介导法将外源人CYP2E1cDNA导入NIH 3T3细胞 ,G4 18筛选后挑取克隆 ,Southernblot鉴定外源基因的整合 ,用不同浓度乙醇和DNP处理阳性克隆 ,RT -PCR和W... 目的 :探讨化学致癌物二亚硝基哌嗪 (DNP)对人CYP2E1异源表达的诱导作用。方法 :脂质体介导法将外源人CYP2E1cDNA导入NIH 3T3细胞 ,G4 18筛选后挑取克隆 ,Southernblot鉴定外源基因的整合 ,用不同浓度乙醇和DNP处理阳性克隆 ,RT -PCR和Westernblotting检测各组细胞CYP2E1表达水平。结果 :获得二个具有外源基因CYP2E1cDNA整合及稳定表达的细胞克隆 ;随着乙醇和DNP处理浓度的提高 ,细胞CYP2E1mRNA和蛋白质水平的表达增强。结论 :DNP与乙醇能稳定诱导CYP2E1异源表达 ,其作用可能与其mRNA转录增强有关 ;DNP致癌可能与CYP2E1对其原位代谢活化相关。 展开更多
关键词 二亚硝基派嗪 细胞色素p4502E1 基因表达
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烟实夜蛾细胞色素P 450 cDNA片段的克隆与序列分析
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作者 李卫华 杨文玲 +2 位作者 苗雪霞 付贵成 郭线茹 《河南农业大学学报》 CAS CSCD 北大核心 2007年第3期284-288,共5页
昆虫细胞色素P 450与昆虫抗药性关系密切,本研究以烟实夜蛾5龄幼虫中肠的总RNA为模板,设计并合成简并引物,利用反转录-多聚酶链式反应(RT-PCR)扩增出了烟实夜蛾细胞色素P 450基因的cDNA片段,将其克隆到pMD 18-T载体进行序列测定,测序得... 昆虫细胞色素P 450与昆虫抗药性关系密切,本研究以烟实夜蛾5龄幼虫中肠的总RNA为模板,设计并合成简并引物,利用反转录-多聚酶链式反应(RT-PCR)扩增出了烟实夜蛾细胞色素P 450基因的cDNA片段,将其克隆到pMD 18-T载体进行序列测定,测序得到的491 bp的片断编码163个氨基酸残基,且该片断在阅读框内.与已公布的谷实夜蛾、棉铃虫和烟芽夜蛾细胞色素P 450氨基酸序列进行比较,其一致性分别为98.7%,98.7%和92.1%. 展开更多
关键词 烟实夜蛾 细胞色素p450 基因克隆 序列分析
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细胞色素P450 CYP4A的组织和细胞表达特异性 被引量:1
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作者 陆刚 唐晓波 +3 位作者 鲍岩岩 余辉艳 郑蕾 朱大岭 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2007年第6期505-511,共7页
目的确定细胞色素P450 CYP4A在组织和细胞水平表达是否具有特异性。方法采用Western印迹法分析细胞色素P450 CYP4A蛋白在培养的牛肺动脉内皮细胞、平滑肌细胞及牛肾动脉内皮细胞的表达;采用原位杂交法检测细胞色素P450 CYP4A mRNA在大... 目的确定细胞色素P450 CYP4A在组织和细胞水平表达是否具有特异性。方法采用Western印迹法分析细胞色素P450 CYP4A蛋白在培养的牛肺动脉内皮细胞、平滑肌细胞及牛肾动脉内皮细胞的表达;采用原位杂交法检测细胞色素P450 CYP4A mRNA在大鼠肺支气管内皮和血管内皮细胞的表达;以14C标记的花生四烯酸(AA)作为反应底物,用荧光高效液相色谱法(HPLC)通过检测牛肺动脉内皮细胞催化外源性AA生成20-羟基廿碳四烯酸(20-HETE)的反应,确定肺动脉内皮细胞是否存在细胞色素P450 CYP4A;将肺动脉内皮细胞破碎并用乙酸乙酯萃取,用荧光物质标记萃取物,用荧光HPLC检测内源性20-HETE,从代谢产物水平确定细胞色素P450 CYP4A的功能蛋白质表达。结果①Western印迹法分析结果表明,细胞色素P450 CYP4A蛋白在牛肺动脉内皮细胞和平滑肌细胞中均有表达,在肺动脉内皮细胞中的表达明显高于平滑肌细胞(积分吸光度值分别为10182±279,5249±167);在牛肾动脉内皮细胞中也有表达,但明显低于肺动脉内皮细胞的表达(积分吸光度值分别为12173±171,17863±207)。②原位杂交结果显示,细胞色素P450 CYP4A mRNA可在大鼠肺支气管内皮细胞和大鼠肺血管内皮均有表达。③用HPLC在牛肺动脉内皮细胞中检测到20-HETE,表明细胞色素P450 CYP4A在肺动脉内皮细胞存在。结论细胞色素P450 CYP4A有其特定的组织和细胞分布,在牛和大鼠肺脏动脉内皮细胞有高表达。 展开更多
关键词 细胞色素p450 cYp4A 细胞 培养的 蛋白表达 基因表达 组织分布
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The effects of CYP1A1 gene polymorphism and p16 gene methylation on the risk of lung cancer in a Chinese population 被引量:2
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作者 Wenhu Tao Yongtang Jin +1 位作者 Zaicheng Yu Xiao Liu 《The Chinese-German Journal of Clinical Oncology》 CAS 2007年第4期350-356,共7页
Objective: To investigate the relationship between the genetic polymorphism of CYP1A1 and the genetic susceptibility to lung cancer as well as to study the effects of the methyiation in p16 gene on the risk of lung c... Objective: To investigate the relationship between the genetic polymorphism of CYP1A1 and the genetic susceptibility to lung cancer as well as to study the effects of the methyiation in p16 gene on the risk of lung cancer in a Chinese population. Methods: A case control study was conducted among 47 cases of lung cancer and 94 controls. The genetic polymorphism of CYP1A1 was tested with method of PCR-RFLP, and a methylation-specific PCR (MSP) was performed to detect p16 methylation. Results: It showed that there was no significant difference in frequencies of the genotypes of CYP1A1 between the two groups (P 〉 0.05). Synergistic effects were not found between smoking and CYP1AI. Methylated p16 gene was found in 44.7% (21/47) of lung cancer tissues and in 17.0% (8/47) of normal lung tissues with significant difference (P 〈 0.05). Conclusion: The genetic polymorphism of CYP1A1 does not increase the risk of lung cancer in a Chinese population. The methylation in p16 gene may be the most common mechanism to inactivate p16 gene in lung cancer, and is not significantly associated with genotype of CYP1A1, 展开更多
关键词 lung neoplasms cytochrome p450 genetic polymorphism p16 gene METHYLATION
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Interactions of chemical carcinogens and genetic variation in hepatocellular carcinoma 被引量:1
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作者 Yu-Jing Zhang 《World Journal of Hepatology》 CAS 2010年第3期94-102,共9页
In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B 1 (AFB 1 ) epoxide reacts ... In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B 1 (AFB 1 ) epoxide reacts with guanine in DNA and can lead to genetic changes. In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB 1 exposure and mutations in the K -ras oncogene are related to vinyl chloride exposure. Numerous genetic alterations accumulate during the process of hepatocarcinogenesis. Chemical carcinogen DNA-adduct formation is the basis for these genetic changes and also a molecular marker which reflects exposure level and biological effects. Metabolism of chemical carcinogens, including their activation and detoxification, also plays a key role in chemical hepatocarcinogenesis. Cytochrome p450 enzymes, N -acetyltransferases and glutathione S -transferases are involved in activating and detoxifying chemical carcinogens. These enzymes are polymorphic and genetic variation influences biological response to chemical carcinogens. This genetic variation has been postulated to influence the variability in risk for HCC observed both within and across populations. Ongoing studies seek to fully understand the mechanisms by which genetic variation in response to chemical carcinogens impacts on HCC risk. 展开更多
关键词 Hepatocellular carcinoma chemical cARcINOGENS AFLATOXIN B 1 pOLYcYcLIc aromatic hydrocarbons 4-aminobiphenyl HEpATITIS B VIRUS HEpATITIS c VIRUS Glutathione S -transferase cytochrome p450 enzymes genetic variation
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Characterization and expression analysis of genes encoding Taxol biosynthetic enzymes in Taxus spp. 被引量:1
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作者 Luyuan Jiang Kaikai Zhang +5 位作者 Xing Lv Liying Yang Shuai Wang Duanfen Chen Yanfang Yang Deyou Qiu 《Journal of Forestry Research》 SCIE CAS CSCD 2021年第6期2507-2515,共9页
Taxol(Paclitaxel),an important anticancer drug,is derived at very low yields from Taxus(yew)species that grow very slowly.In the present study,thirteen genes that encode enzymes involved in Taxol biosynthesis in Taxus... Taxol(Paclitaxel),an important anticancer drug,is derived at very low yields from Taxus(yew)species that grow very slowly.In the present study,thirteen genes that encode enzymes involved in Taxol biosynthesis in Taxus spp.were analyzed with bioinformatics methods,and their expression levels in different tissues and after cold and hormone treatments were also analyzed.The results indicated that many cis-elements related to abiotic stresses and hormones were found in the promoter sequences of the 8 genes involved in Taxol biosynthesis.Moreover,the 13 enzymes encoded by the target genes were located in different organelles and had many phosphorylation sites in the response proteins.The 13 genes were expressed highly either in roots or in stems,with lower transcripts in needles,and they were highly expressed after treatment with cold,gibberellin,methyl jasmonate or coronatine,consistent with predictions based on the bioinformatics analysis.These results suggest that the factors such as hormones and abiotic stresses stimulate taxane biosynthesis in yews,providing an important way to sustainably generate taxanes from yew trees or their cell cultures to improve Taxol yields. 展开更多
关键词 gene expression Bioinformatics analysis Acyltransferase cytochrome p450 Abiotic stress Hormone
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Role of CYP2E1 gene polymorphisms association with hepatitis risk in Northeast India
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作者 Manab Deka Moumita Bose +7 位作者 Bharati Baruah Purabi Deka Bose Subhash Medhi Sujoy Bose Anjan Saikia Premashish Kar Subhash Medhi Sujoy Bose 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第38期4800-4808,共9页
AIM:To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS:A total of 104 jaundice patients and 124 community c... AIM:To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS:A total of 104 jaundice patients and 124 community controls were included. Serological analysis was performed by routine enzyme-linked immunosorbent assay, and nucleic acid testing for hepatitis viruses was done by polymerase chain reaction (PCR), followed by PCR direct sequencing for viral genotyping. Cytochrome P450 2E1 (CYP2E1) polymorphism was studied by PCR-restriction fragment length polymorphism. Nitrite and volatile nitrosamines in indigenous foods consumed routinely by the Northeast Indian ethnic population were estimated by Griess’s reagent and GC-MS, respectively.RESULTS: Hepatitis A virus (HAV) infection was predominantly prevalent (36.5%) in our cohort, followed by hepatitis B virus (HBV), hepatitis E virus (HEV) andhepatitis C virus. HBV genotype D and HEV genotype 1 were the most dominant. CYP2E1 c1/c2 genotype frequency was comparatively higher in alcoholic (P<0.0001,OR =30.5) and cryptogenic (P=0.014, OR=8.714) patients, and was associated with significantly higher hepatitis risk (P=0.0.007,OR=6.489). Mutant C allele of Cyp2E1 DraⅠ frequency was comparatively higher in HAV (P=0.006), alcoholic (P =0.003) and cryptogenic (P=0.014) cases, and was associated with overall hepatitis risk (P=0.026, OR=5.083). Indigenous foods, Gundruk, Kharoli, betel leaf and nuts were found to have the highest nitrite content. CONCLUSION: Apart from viral factors, CYP2E1 polymorphism might be associated with increased risk of liver diseases in Northeast India. Indigenous foods that contain nitrite and nitrosamine might be an associated risk factor. 展开更多
关键词 Viral hepatitis cytochrome p450 2E1 gene polymorphism NITRITES NITROSAMINES
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CYP1A1多态性与肺癌遗传易感性的关系 被引量:7
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作者 李代蓉 周清华 +4 位作者 郭占林 袁天柱 朱文 王艳萍 陈晓禾 《中华肿瘤防治杂志》 CAS 2006年第23期1765-1768,共4页
目的:探讨代谢酶基因CYP1A1基因多态性与中国汉族人群肺癌遗传易感性之间的相关性。方法:应用AS-PCR技术检测150例中国四川汉族肺癌和152例中国四川汉族健康人的CYP1A1基因Exon 7多态性分布频率,并分析了Exon 7多态性与中国四川汉族... 目的:探讨代谢酶基因CYP1A1基因多态性与中国汉族人群肺癌遗传易感性之间的相关性。方法:应用AS-PCR技术检测150例中国四川汉族肺癌和152例中国四川汉族健康人的CYP1A1基因Exon 7多态性分布频率,并分析了Exon 7多态性与中国四川汉族人群肺癌遗传易感性之间的相关性。结果:CYP1A1 Exon 7 3种多态基因型分布频率在两组间比较差异无统计学意义,X^2=0.634,P=0.728。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺癌的危险性增加。OR=1.139,95%CI为0.635~2.042,P=0.662。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺鳞癌的风险显著增加,OR=3.510,95%CI=1.326-9.293,P=0.011。结论:Val突变等位基因可能是中国四川汉族人群的肺癌易感基因。CYP1A1基因Exon 7多态性在肺鳞癌发生中起重要作用。 展开更多
关键词 肺肿瘤 多态现象 遗传 代谢 酶类 基因 细胞色素p450 cYp1A1
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细胞色素P450酶4F2基因多态性对中国人服用华法林起始七天内剂量的影响 被引量:12
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作者 熊筱伟 刘红 +4 位作者 韩璐璐 娄莹 华潞 李彦 李一石 《中国循环杂志》 CSCD 北大核心 2014年第11期910-912,共3页
目的:研究细胞色素P450酶4F2(CYP4F2,rs2108622)基因多态性对中国汉族人群服用华法林起始七天内剂量的影响。方法:利用Real-time PCR的方法分析271例服用华法林抗凝患者的CYP4F2基因多态性,记录患者服用华法林七天内的平均华法林初始剂... 目的:研究细胞色素P450酶4F2(CYP4F2,rs2108622)基因多态性对中国汉族人群服用华法林起始七天内剂量的影响。方法:利用Real-time PCR的方法分析271例服用华法林抗凝患者的CYP4F2基因多态性,记录患者服用华法林七天内的平均华法林初始剂量,国际标准化比值(INR)首次进入治疗窗的时间。统计学方法分析CYP4F2基因多态性的CC,CT和TT各基因型间初始剂量和INR首次进入治疗窗的时间差异。结果:CYP4F2基因多态性的TT、CT/TT基因型的平均华法林初始剂量显著高于CC基因型(P<0.05),差异具有统计学意义。TT基因型的INR首次进入治疗窗的时间显著高于CC基因型(P<0.05),差异具有统计学意义。除外患者性别,年龄,身高,体重,CYP2C9和VKORC1基因多态性以及合并疾病和合用药等多种因素,CYP4F2基因多态性对患者华法林起始七天内华法林剂量的影响仍有统计学意义(回归系数0.21,P=0.003)。结论:在服用华法林的中国人中,CYP4F2基因多态性对华法林起始七天内的剂量有影响。 展开更多
关键词 华法林 cYp4F2基因多态性 初始剂量
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pcDNA3.1(+)-CYP19-GFP真核表达质粒构建 被引量:5
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作者 邵喜英 陈占红 +2 位作者 曹江 方永明 王晓稼 《浙江大学学报(医学版)》 CAS CSCD 北大核心 2011年第2期189-194,共6页
目的:构建pcDNA3.1(+)-CYP19-GFP、pcDNA3.1(+)-CYP19W39R-GFP、pcDNA3.1(+)-CYP19R264C-GFP与pcDNA3.1(+)-CYP19W39R-R264C-GFP真核表达质粒,并观察pcDNA3.1(+)-CYP19-GFP质粒在MCF-7和Bcap-37细胞中的表达。方法:①采用RT-PCR技术扩增... 目的:构建pcDNA3.1(+)-CYP19-GFP、pcDNA3.1(+)-CYP19W39R-GFP、pcDNA3.1(+)-CYP19R264C-GFP与pcDNA3.1(+)-CYP19W39R-R264C-GFP真核表达质粒,并观察pcDNA3.1(+)-CYP19-GFP质粒在MCF-7和Bcap-37细胞中的表达。方法:①采用RT-PCR技术扩增CYP19 cDNA,插入pcDNA3.1(+)载体中,构建pcDNA3.1(+)-CYP19表达质粒;酶切pcDNA3.1(+)-CYP19(304bp BamHⅠ)-GFP和pcDNA3.1(+)-CYP19质粒,构建pcDNA3.1(+)-CYP19-GFP表达质粒;②以pcDNA3.1(+)-CYP19-GFP质粒为模板,采用定点突变技术,构建pcDNA3.1(+)-CYP19W39R-GFP和pcDNA3.1(+)-CYP19R264C-GFP及pcDNA3.1(+)-CYP19W39R-R264C-GFP表达质粒;③pcDNA3.1(+)-CYP19-GFP质粒通过脂质体介导转染MCF-7和Bcap-37细胞,荧光显微镜观察其在细胞中的表达。结果:①酶切鉴定及测序验证pcDNA3.1(+)-CYP19-GFP构建成功;②测序验证pcDNA3.1(+)-CYP19W39R-GFP和pcDNA3.1(+)-CYP19R264C-GFP及pcDNA3.1(+)-CYP19W39R-R264C-GFP构建成功;③在经转染的MCF-7和Bcap-37细胞中观察到较强的绿色荧光。结论:pcDNA3.1(+)-CYP19-GFP、pcDNA3.1(+)-CYP19W39R-GFP和pcDNA3.1(+)-CYP19R264C-GFP及pcDNA3.1(+)-CYP19W39R-R264C-GFP真核表达质粒已成功构建,并证实pcDNA3.1(+)-CYP19-GFP质粒能在MCF-7和Bcap-37细胞中表达,为进一步研究CYP19基因单核苷酸多态性的确切功能奠定基础。 展开更多
关键词 细胞色素p450酶系统/遗传学 质粒 遗传载体 真核细胞 cYp19基因 真核表达质粒 GFp
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等位基因特异性PCR检测CYP3A5和MDR-1基因多态性方法的建立及临床应用 被引量:2
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作者 吴洁 侯佳展 +4 位作者 程倩 李佳垚 李丹丹 尹逸丛 苏薇 《临床检验杂志》 CAS CSCD 2017年第11期844-848,共5页
目的用等位基因特异性PCR(ARMS-PCR)检测细胞色素P450酶CYP3A5(A6986G)和多药耐药基因MDR-1(C3435T)基因多态性,探讨其与肾移植受者他克莫司(Tac)血药浓度和剂量比的相关性。方法根据CYP3A5(A6986G)和MDR-1(C3435T)基因多态性位点分别设... 目的用等位基因特异性PCR(ARMS-PCR)检测细胞色素P450酶CYP3A5(A6986G)和多药耐药基因MDR-1(C3435T)基因多态性,探讨其与肾移植受者他克莫司(Tac)血药浓度和剂量比的相关性。方法根据CYP3A5(A6986G)和MDR-1(C3435T)基因多态性位点分别设计ARMS-PCR引物,分析72例肾移植受者外周血基因组DNA中该2个基因位点的多态性,同时以DNA测序法为金标准进行验证。化学发光微粒子免疫分析法测定肾移植受者血Tac浓度,并比较术后1个月时不同基因型受者之间血Tac浓度、Tac剂量/Tac用量的差异。结果建立的ARMS-PCR法与DNA测序法检测符合率为100%。72例肾移植受者中,CYP3A5*1/*1、*1/*3和*3/*3基因型的发生频率分别为18.1%、31.9%和50.0%,MDR-1 C/C、C/T和T/T基因型的发生频率分别为27.8%、58.3%和13.9%。此外,不同CYP3A5基因型肾移植受者的血Tac浓度(P=0.014)和Tac浓度/Tac用量(P=0.019)均存在明显差异,进一步两两比较发现,CYP3A5*3/*3基因型受者血Tac浓度/Tac用量明显高于*1/*1和*1/*3基因型(P均<0.05)。结论成功建立检测CYP3A5和MDR-1基因多态性的ARMS-PCR法,肾移植受者CYP3A5*3基因多态性与Tac的药代动力学明显相关。 展开更多
关键词 等位基因特异性pcR 细胞色素p450cYp3A5 多药耐药基因MDR-1 基因多态性
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细胞色素P4501A1基因多态性与喉癌遗传易感性的研究 被引量:1
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作者 雷大鹏 潘新良 +4 位作者 郭辰虹 栾信庸 许风雷 张立强 刘大昱 《中华耳鼻咽喉科杂志》 CSCD 北大核心 2002年第5期373-376,共4页
目的 探讨细胞色素P45 0 1A1(cytochromep45 0 1A1,CYP1A1)MspI多态性与喉癌易感性之间的关系。方法 以病例 对照研究 ,采用聚合酶链反应 限制性片段长度多态性分析 (polymerasechainreactionrestrictionfragmentlengthpolymorphism ,... 目的 探讨细胞色素P45 0 1A1(cytochromep45 0 1A1,CYP1A1)MspI多态性与喉癌易感性之间的关系。方法 以病例 对照研究 ,采用聚合酶链反应 限制性片段长度多态性分析 (polymerasechainreactionrestrictionfragmentlengthpolymorphism ,PCR RFLP)方法检测 6 2例喉鳞状细胞癌和 5 6例健康对照CYP1A1的基因型 ,并按吸烟指数 (smokingindex ,SI,吸烟支数 /d×吸烟年数 )的不同分析患喉癌风险。结果 CYP1A1MspI分为野生型A、突变杂合型B和突变纯合型C的 3种基因型。杂合型B和突变纯合型C在病例组分别占 5 8 1%和 14 5 % ,对照组分别占 39 3%和 7 1% ,两两比较 ,病例组杂合型B、纯合型C显著高于对照组 ,P <0 0 5 ,比值比率 (oddsration ,OR)分别为 2 89(95 %可信限1 31~ 6 37)和 3 97(95 %可信限 1 10~ 14 2 8)。在低吸烟量组 (SI≤ 40 0 )和高吸烟剂量组 (SI >40 0 )中 ,纯合型C的OR值分别为 4 5 (95 %可信限 0 6 4~ 31 6 1)和 9(95 %可信限 1 6 0~ 5 0 74)。结论 CYP1A1MspI多态性与吸烟协同在喉癌的发生、发展中可能起重要作用。突变纯合型个体患喉癌风险增加 ,吸烟时间越长 ,量越大 。 展开更多
关键词 喉肿瘤 鳞状细胞癌 基因 细胞色素p-450 cYp1A1 吸烟 疾病遗传易感性
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CYP2D6基因与药物代谢 被引量:4
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作者 施安国 《中国新药与临床杂志》 CAS CSCD 北大核心 2003年第8期491-494,共4页
细胞色素P 45 0 (CYP)中的CYP2D6酶在抗抑郁药、安定药及某些抗心律失常药的代谢中起重要作用 ,CYP2D6基因位于 2 2号常染色体上为隐性遗传 ,CYP2D6基因呈多态性约有 70余种等位基因变异型 ,也存在特异人群差别 ,因而导致所编码的酶活... 细胞色素P 45 0 (CYP)中的CYP2D6酶在抗抑郁药、安定药及某些抗心律失常药的代谢中起重要作用 ,CYP2D6基因位于 2 2号常染色体上为隐性遗传 ,CYP2D6基因呈多态性约有 70余种等位基因变异型 ,也存在特异人群差别 ,因而导致所编码的酶活性不同 ,这些数据有助于理解药物代谢的个体差异、有助于预测药物之间的相互作用。 展开更多
关键词 细胞色素p-450 cYp2D6基因 药物代谢 基因多态性
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CYP2E1基因多态性与肝癌易感性的关系 被引量:5
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作者 姜爱仁 吴建中 +5 位作者 丁建华 李苏平 曹海霞 苏平 高长明 周学富 《肿瘤防治杂志》 2004年第5期464-466,共3页
目的 :研究细胞色素P45 0 2E1(CYP2E1)基因多态性与肝癌易感性的关系。方法 :在肝癌高发区泰兴市进行病例对照研究 ,调查研究对象的饮酒习惯 ,以PCR RFLP方法分析CYP2E1基因型。结果 :肝癌病例组与对照组中CYP2E1变异基因型 (C1/C2 +C2 ... 目的 :研究细胞色素P45 0 2E1(CYP2E1)基因多态性与肝癌易感性的关系。方法 :在肝癌高发区泰兴市进行病例对照研究 ,调查研究对象的饮酒习惯 ,以PCR RFLP方法分析CYP2E1基因型。结果 :肝癌病例组与对照组中CYP2E1变异基因型 (C1/C2 +C2 /C2 )的分布频率分别为 41 0 6%和 3 7 0 2 % ,两者差异无统计学意义 ;从饮酒习惯等方面分析 ,携带CYP2E1变异基因型的饮酒者与携带野生基因型的不饮酒者间患肝癌危险性差异无统计学意义。结论 展开更多
关键词 多态现象(遗传学) 肝肿瘤/遗传学 基因频率 基因型 细胞色素p-450-cYp2E1/遗传学 饮酒
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