细胞色素P450 1A1在自然流产患者胎盘绒毛组织中的表达及意义

目的　探讨细胞色素P4 5 0 1A1(CYP1A1)mRNA在自然流产患者胎盘绒毛组织中的表达及其意义。方法　采用半定量逆转录聚合酶链反应 (RT -PCR)法检测 4 5例自然流产患者 (研究组 )中及 30例正常妊娠孕妇 (对照组 )胎盘绒毛组织中CYP1A1mRNA的表达。结果　自然流产及正常妊娠胎盘绒毛组织中CYP1A1mRNA相对表达强度分别为 0 .5 6± 0 .2 0、0 .35± 0 .14、两组比较差异显著 (P <0 .0 1)。自然流产患者中孕期有被动吸烟及孕期有饮茶或咖啡习惯者的胎盘绒毛组织中CYP1A1mRNA表达最强。结论　胎盘绒毛组织中CYP1A1mRNA表达增强可能与自然流产的发生相关 ,同时可在一定程度上说明孕妇吸烟、被动吸烟及摄入过多咖啡因可通过增强胎盘绒毛组织中CYP1A1的转录水平而增加自然流产的风险。     

CYP1A1基因多态性与急性淋巴细胞白血病的关系

目的　探讨CYP1A1基因多态性与急性淋巴细胞白血病 (ALL)遗传易感性的关系。方法　应用PCR -RFLP、ASA技术 ,分析 78例ALL患者和 112例健康人CYP1A1基因多态性 ,比较ALL患者与对照组间频率差异。结果　ALL组CYP1A1MspI基因多态位点 ,各等位基因和基因型频率与对照组比较有显著性差异 (P <0 .0 5 ) ,其中等位基因m2使患ALL的危险度提高了 1.5 4倍 ,m1m2、m2m2基因型使患ALL的危险度分别提高了 2 .2 7倍和 2 .77倍 ;ALL组CYP1A1Ile-Val各等位基因和基因型频率与对照组比较无显著性差异 (P >0 .0 5 )。结论　CYP1A1MspI基因多态可能与ALL的发生有关。     

CYP1A1基因多态性与妊娠期肝内胆汁淤积症相关性研究

目的 探讨参与雌激素代谢的细胞色素P4501A1(cytochrome P450 1A1,CYPlA1)基因多态性与成都地区妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)的关系.方法 分别应用聚合酶链反应.限制性片段长度多态性技术和等位基因特异性PCR技术,对100例ICP患者和100名正常对照孕妇CYP1A1基因Msp I位点和Ile/Val位点多态性进行分析.结果 Msp I位点多态性在ICP组和对照组中的分布差异无统计学意义(P》0.05),而ICP组含Val等位基因的Ile/Val和Val/Val基因型增加ICP的发病风险(P=0.047,OR=1.768).结论 CYP1A1基因第7外显子的Ile/Val基因多态性可能与成都地区ICP易感性有关;而Msp I位点多态性与ICP的发生无相关性.     

CYP1A1、NAT2基因多态性与帕金森病的关系

为探讨代谢酶基因多态与帕金森病 (ＰＤ)易患性的关系 ,我们应用ＰＣＲ ＲＦＬＰ、ＡＳＡ和自动实时荧光Ｌｉｇｈｔ Ｃｙｃｌｅｒ技术对 90例ＰＤ患者的ＣＹＰ1Ａ1ＭｓｐＩ基因型和第 7外显子4 889位异亮氨酸 (Ｉｌｅ) 缬氨酸 (Ｖａｌ)基因型及Ｎ 乙酰基转移酶 2(ＮＡＴ 2 )基因 4个多态 :第 4 81位点的 (Ｃ→Ｔ) [ＮＡＴ 2 5Ａ];第5 90位点的 (Ｇ→Ａ) [ＮＡＴ2 6Ａ];第 85 7位点的 (Ｇ→Ａ)[ＮＡＴ2 7Ａ/Ｂ]和第 191位点的 (Ｇ→Ａ) [ＮＡＴ2 14Ａ]进行检测和分析1　对象和方法1.1　对象　ＰＤ患者 90例 (早发ＰＤ患者 4 2例 ,男 2 2…     

温州地区汉族正常人群CYP1A2基因多态性分布特征

目的检测CYP1A2基因多态性在温州地区汉族正常人群的分布特征。方法采用聚合酶链反应（PCR）产物直接测序法检测108例随机血液样本DNA中CYP1A2基因序列单核苷酸多态性位点（SNP）的分布。对检测到的3个多态位点2159G〉A、3613T〉C、5347C〉T,进一步采用PCR技术分析472例正常人位点的基因型频率和等位基因频率。结果 （1）2159 G〉A位点：G和A等位基因的频率分别为93.8%,6.2%,GG、GA、AA基因型频率分别为87.7%、12.1%、0.2%（χ2=0.325,P〉0.05）;（2）3613 T〉C位点：T和C等位基因的频率分别为97.9%、2.3%,TT、TC、CC基因型频率分别为95.3%、4.4%、0.3%（χ2=0.298,P〉0.05）;（3）5347 C〉T位点：C和T等位基因的频率分别为87.9%、12.1%。CC、CT、TT基因型分布频率分别为77.8%、20.3%、1.9%（χ2=0.742,P〉0.05）;（4）2159 G〉A、5347 C〉T组成的单倍型频率为3.2%。结论温州地区汉族正常人群CYP1A2基因存在2159G〉A、3613T〉C、5347C〉T多态位点。     

细胞色素P450 1A1的研究进展

细胞色素P450酶系参与生物体内许多内源性及外源性物质的生物转化。其中细胞色素 P4501A1(CYP1A1)广泛存在于多种肝外组织,参与了多种前致癌物和致突变物的活化代谢过程,并与 多种肿瘤发生相关。本文综述了CYP1A1在体内的分布、诱导和抑制,遗传多态性及癌症易感性,简要 介绍了该领域研究的进展情况。     

CYP1A1和GSTM1基因多态性与BPDE-DNA加合物的关系及其对肺癌的影响

目的 分析代谢酶基因细胞色素氧化酶P450(cytochrome P450,CYP450)1A1与谷胱苷肽硫转移酶M1(glutathione S-transferase μ1,GSTM1)的多态性和二羟环氧苯并芘(benzo A-pyrene-diolepoxide,BPDE)-DNA加合物之间的关系,并探讨其对肺癌发病的影响.方法 用病例-对照方法收集200例原发性肺癌患者的流行病学调查资料及外周血样本,采用限制性片段长度多态性-PCR法检测血中CYP1A1、GSTM1基因多态性,应用竞争性酶联免疫吸附法检测BPDE-DNA加合物浓度.结果 CYP1A1变异型吸烟者、GSTM1缺失型吸烟者患肺癌风险升高,OR值分别为2.406(1. 321～4. 382)和2.755(1.470～5.163).肺癌患者BPDE-DNA加合物浓度高于对照人群,且肺癌吸烟者加合物浓度明显高于肺癌不吸烟者(P=0.0252);GSTM1缺失型个体DNA加合物水平高于5.0加合物/108核苷酸时,患肺癌的风险升高(OR=1.988,95％ CI:1.011～3.912);CYP1A1变异型吸烟者形成高水平DNA加合物的风险明显高于CYP1A1野生型不吸烟者(P=0.0459); GSTM1缺失型吸烟者形成高水平DNA加合物的风险高于GSTM1功能型不吸烟者(OR=2.432,95％ CI:1.072～4.517).结论 GSTM1缺失型个体DNA加合物水平高更容易增加肺癌危险性;CYP1A1变异型吸烟者、GSTM1缺失型吸烟者更容易形成高水平的DNA加合物,对肺癌的发生可能有重要影响.     

CYP1A1-Hinc和GSTT1基因遗传多态性与原发性痛经关系分析

目的　研究原发性痛经的遗传易感性。方法　收集某纺织厂 499名新婚女工的资料 ,采用L ogistic回归分析 ,评价 CYP1A1- Hinc 和 GSTT1多态性与重度原发性痛经的关系。结果　在未调整环境因素时 CYP1A1- Hinc 变异基因型虽对痛经有缓解趋势 ,但差异无显著性 (CYP1A1- Hinc :OR=0 .6 495 % CI:0 .35～ 1.17)。而 GSTT1变异基因型可增加重度原发性痛经危险性 (GSTT1:OR=1.83,95 % CI:1.0 4～ 3.2 1)。调整潜在环境影响因素后 ,CY1A1- Hinc 变异基因型显示对原发性痛经有缓解趋势(CYP1A1- Hinc :OR=0 .5 8,95 % CI:0 .31～ 1.0 8) ,但差异仍无显著性。而 GSTT1变异基因型仍显示可增加重度原发性痛经的危险性 (GSTT1:OR=2 .0 1,95 % CI:1.12～ 3.6 2 )。结论　重度原发性痛经与GSTT1遗传多态性相关     

中国北方汉族人细胞色素P4501 A1基因MspⅠ多态性的研究

目的　探讨中国北方汉族人细胞色素P(cytochromeP ,CYP) 4 5 0 1A1基因MspⅠ多态性。方法　用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)技术 ,分析了 172名北方汉族正常健康成人CYP1A1基因 3′端限制性内切酶MspⅠ位点的3种基因型 (A、B、C)的分布频率。结果　MspⅠ等位基因m1、m2分别占 6 0 8%、39 2 %。MspⅠ基因型A占 34 9% ,基因型B占 5 1 7% ,基因型C占 13 4 %。结论　本研究结果提示中国北方汉族人解毒酶CYP1A1基因存在MspⅠ多态性。     

中国北方汉族人细胞色素P450 1A1基因MspⅠ多态性与早发性帕金森病关系的研究

目的：探讨中国北方汉族人细胞色素P4501A1基因MspI多态性与早发性帕金森病的易感性的关系。方法：用聚合酶链反应－限制性片段长度多态性技术,分析了126例早发性帕金森病患者（发病年龄＜50岁）和172名正常健康成人CYP1A1基因3’端限制性内切酶MspI位点的3种基因型（A、B、C）的分布频率。结果：MspI基因型C在病例组和对照组中各占15．1％和13．4％,基因型A在两组中分别占41．3％和34．9％,基因型B在两组中分别占43．6％和51．7％,各基因型在两组中相比较,差异无显著性（P＞0．05）。C基因型在病例组和对照组分别占36．9％和39．2％,两者差异无显著性（P＞0．05）。结论：提示解毒酶CYP1A1基因MspI多态性的单独存在可能与早发性帕金森病的易患性无关。     

Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not involved in the risk of recurrent pregnancy loss

The etiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the relation between RPL and polymorphisms in four genes, human aryl hydrocarbon (Ah) receptor, cytochrome P450 (CYP) 1A1, CYP1A2 and CYP1B1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. All cases and controls were women resident in Sapporo, Japan and the surrounding area. The Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotypes were assessed in 113 Japanese women with recurrent pregnancy loss (RPL) and 203 ethnically matched women experiencing at least one live birth and no spontaneous abortion (control). No significant differences in Ah receptor, CYP1A1, CYP1A2 and CYP1B1 genotype frequencies were found between the women with RPL and the controls [Ah receptor: Arg/Arg (reference); Arg/Lys and Lys/Lys, odds ratio (OR)=0.67; 95% confidence interval (CI)=0.40-1.11, CYP1A1: m1m1 (reference); m1m2 and m2m2, OR = 0.86; 95% CI = 0.53-1.40, CYP1A2: C/C and C/A (reference); A/A, OR = 1.16; 95% CI = 0.71-1.88, CYP1B1: Leu/Leu (reference); Leu/Val and Val/Val, OR = 1.18; 95% CI = 0.68-2.02]. The present study suggests that the Ah receptor, CYP1A1, CYP1A2 and CYP1B1 gene polymorphisms are not major genetic regulators in RPL.     

Analysis of human CYP1A1 and CYP1A2 genes and their shared bidirectional promoter in eight world populations

The human CYP1A1_CYP1A2 locus comprises the CYP1A1 (5,988 bp) and CYP1A2 (7,759 bp) transcribed regions, oriented head‐to‐head, sharing a bidirectional promoter of 23,306 bp. The older CYP1A1 gene appears more conserved and responsible for critical life function(s), whereas the younger CYP1A2 gene might have evolved more rapidly due to environmental (dietary) pressures. A population genetics study might confirm this premise. We combined 60 CYP1A1_CYP1A2 SNPs found in the present study (eight New Guinea Highlanders, eight Samoans, four Dogrib, four Teribe, four Pehuenche, and one Caucasian) with those found in a previous study (six West Africans, four Han Chinese, six Germans, four Samoans, and four Dogrib), yielding a total of 106 SNPs in 106 chromosomes. Resequencing of Oceanians plus Amerindians in the present study yielded 21 New World SNPs (～20%), of which 17 are not previously reported in any SNP database. Various tests revealed selective pressures for both genes and both haploblocks; unfortunately, differences in rates of evolution between the two genes were undetectable. Fay & Wu's H test revealed a “hitchhiking event” centered around four SNPs in the CYP1A1 3′‐UTR; a study in silico identified different microRNA‐binding patterns in the hitchhiked region, when the mutations were present compared with the mutations absent. Hum Mutat 30:1–14, 2009. © 2009 Wiley‐Liss, Inc.     

CYP3A5 3, CYP3A4 1B and MDR1 C3435T genotype distributions in Ecuadorians

Polymorphisms in CYP3A genes, such as CYP3A5} and CYP3A4, as well as in the MDR1 gene, which encodes for P-glycoprotein, have been implicated as genetic markers in several disorders. Differences in the frequency distribution of the allelic variants CYP3A5 3, CYP3A4 1B, and MDR1 3435T have been demonstrated between distinct ethnic groups. In this study we examined the frequency of these allelic variants in 317 healthy Mestizo individuals from Ecuador and made comparisons with results reported in the literature. The genotypes were determined by PCR-RFLP. Allele and genotype differences were studied by chi-square test. The MDR1 T allele frequency was similar to that of Spaniard or Asian populations, which is consistent with the ethnic origin of Ecuadorian Mestizo individuals (Amerindian and Spaniard Caucasians). By contrast, the CYP3A5 3 allele frequency was significantly lower in Ecuadorians than in Spaniards and other white populations and higher than in Central Americans, Asians and blacks. CYP3A4 1B was more common in Ecuadorians than in Caucasian or Asian populations but less present than in blacks. The differences in the polymorphism found in this work should be considered in allele-disease association studies.     

CYP1A1、CYP2D6基因多态性对白血病发生的影响

目的 分析细胞色素P450 CYP1A1和CYP2D6的多态性基因型在湖南地区白血病患者和健康人群中的分布及其对白血病发生的影响.方法 采用PCR及PCR-RFLP技术分析多态性基因型频率.结果 CYP1A1和CYP2D6基因的野生型、杂合突变型及纯合突变型的分布频率在急性淋巴细胞性白血病、急性非淋巴细胞性白血病、慢性粒细胞性白血病患者组与健康对照组之间无显著性差异;携带一个突变等位基因型的个体患白血病的风险与相应野生型携带者比较均无显著性差异;急性非淋巴细胞性白血病患者组的CYP1A1杂合突变型与CYP2D6杂合突变型的联合基因型频率高于健康对照组.结论 单独的CYP1A1或CYP2D6基因的多态性变异与白血病易感性不相关;CYP1A1杂合突变与CYP2D6杂合突变的联合基因型增加患急性非淋巴细胞性白血病的风险.     

韩国人CYP450 1A1、CYP450 2E1和GSTM1、GSTT1、GSTP1基因座遗传多态性分析

目的 调查代谢相关的CYP4501A1、CYP4502E1和GSTM1、GSIT1、GSTP1基因座在韩国人群中的遗传多态性分布状况。方法 采用多重聚合酶链式反应、聚合酶链式反应-限制性片段长度多态性技术，分析300名韩国健康大学生的CYP1A1基因3′端限制性内切酶Msp Ⅰ位点、CYP2E1基因5′端转录调节区Pst Ⅰ位点和GSTM1、GSTT1缺失与存在、GSTP1基因第5外显子BsmA Ⅰ位点的基因型，计算基因型和基因频率。结果 CYP1A1基因型频率为ml／ml型39．7％、ml／m2型49．7％、m2／m2型10．7％，基因频率为ml 0．645、m2 0．355。CYP2E1基因型频率为cl／cl型66．7％、cl／c2型30％、c2／c2型3．3％，基因频率为C1 0．818、C2 0．182。GSTM1基因缺失型频率为53．3％。GSTT1基因缺失型频率为54．7％。GSTP1基因型频率为Ile／Ile型62％、Ile／Val型34．3％、VaL／Val型3．7％，基因频率为Ile 0．792、Val 0．208。基因分布符合Hardy-Weirtberg平衡定律。结论 韩国人CYP1A1、CYP2E1、GSTM1、GSTT1基因分布与我国人群较为相近，半数以上人缺乏GSTM1和GSTT1基因，纯合缺失型频率超过印度人的3倍。     

CYP1A1 genetic polymorphisms in Ecuador, South America

A total of 108 individuals from the Ecuadorian population from rural and urban places were analyzed for two CYP1A1 gene polymorphisms. The frequency of the val allele at codon 462 was 0.50, while the frequency of the Msp I restriction site, m2 allele at the T6235C position was 0.70. These polymorphisms in Ecuador have higher frequencies if we compare with others around the world, with the exception of some South American population in Brazil and Chile.     

CYP1A1基因I462V多态与非小细胞肺癌的相关性

目的 探讨CYP1A1基因1462V多态性与非小细胞肺癌的相关性.方法 采用病例对照研究,应用聚合酶链反应-限制性片段长度多态性对72例非小细胞肺癌患者(病例组)和90例正常对照(对照组)CYP1A1基因I462V多态进行检测,分析基因型频率和等位基因频率在病例组和对照组的分布,比较不同基因型与非小细胞肺癌患病风险的关...     

Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects

Genetic susceptibility to tobacco smoke might have relation to adverse pregnancy outcomes. To estimate the effects of maternal smoking and genetic polymorphisms on infant birth weight and length, we conducted a prospective cohort study of 293 women who delivered singleton live births in Sapporo, Japan. Birth weight and length were significantly lower among infants born to continuously smoking women having the aryl hydrocarbon receptor (AhR) wild type genotype (Arg/Arg; 211 g +/- 76 g; 1.2 cm +/- 0.4 cm, p < 0.01 and p < 0.01, respectively), the CYP1A1 variant genotype (m1/m2 + m2/m2; 170 g +/- 64 g, 0.8 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively), or the GSTM1 null genotype (171 g +/- 58 g, 0.6 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively). When combinations of these genotypes were considered, birth weight and length were significantly lower for infants of continuously smoking women in the AhR wild type + CYP1A1 variant group (315 g +/- 116 g; 1.7 cm +/- 0.6 cm, p < 0.01 and p < 0.01, respectively) and in the CYP1A1 variant + GSTM1 null group (237 g +/- 92 g; 1.3 cm +/- 0.5 cm, p < 0.05 and p < 0.01, respectively). These genotypes did not confer adverse effects among women who had never smoked; therefore, maternal smoking in combination with maternal AhR, CYP1A1 and GSTM1 genetic polymorphisms may adversely affect infant birth size.     

细胞色素P45A1基因变异与肺癌易患性

Individual susceptibility to cancer induced by environmental agents may be influenced by polymorphic metabolic genes responsible for the activation or detoxification of carcinogens．The association between genetic polymorphisms in cytochrome P4501A1 (CYP1A1) and lung cancer susceptibility has been extensively studied．The various CYP1A1 alleles exhibit population frequencies that depend on race and ethnicity．An increased risk of lung cancer in Asians was found to be associated with genetic polymorphisms in CYP1A1．However,reports from Caucasians are not consistant,probably suggesting the ethnic-sepecific effect of the polymorphisms in the locus on the cancer．Evidence also exists for the association between levels of carcinogen-DNA adducts or frequency of oncogene and tumor suppressor gene mutations and CYP1A1 polymorphisms．These findings provide a better understanding of the relationship between CYP1A1 and lung cancer susceptibility．