CYP1A1基因多态性与子宫内膜癌易感性关系的研究

目的:研究细胞色素P4501A1(CYP1A1)基因MspⅠ位点多态性与子宫内膜癌发生的关系。方法:用PCR-RFLP法检测174例子宫内膜腺癌患者和114例对照者CYP1A1基因MspI位点多态性。结果:合并杂合型T/C和突变型C/C后与野生型T/T比较,两组差异有统计学意义(P=0.047,OR=1.635)。在绝经年龄<50岁的病例组,T和C等位基因频率与对照组相比差异有统计学意义(P=0.032);初潮年龄≤14岁,等位基因频率在两组中差异有统计学意义(P=0.036);经BMI分层分析,未发现MspI多态性与子宫内膜癌有关。结论:CYP1A1基因MspI多态中突变等位基因C可显著增加子宫内膜癌的发病风险,且绝经年龄越早、初潮年龄越早携带等位基因C的个体越易感子宫内膜癌。     

CYP1A1 MspI多态性及其合并GSTM1基因缺失与子宫内膜异位症的关系

目的:探讨新疆维吾尔族、汉族人群中解毒酶细胞色素P4501A1(CYP1A1)基因MspI多态性、CYP1A1/MspI合并GSTM1基因缺失基因型与子宫内膜异位症(内异症)的关系。方法:用聚合酶链反应限制性片段长度多态性技术,检测维吾尔族107例正常妇女与41例内异症患者、汉族105例正常妇女与80例内异症患者CYP1A1基因限制性内切酶MspI位点的3种基因型的分布频率。结果:CYP1A1基因MspI位点基因型在维吾尔族正常对照组的分布频率为TT(48.6%)、TC(42.9%)、CC(8.5%),等位基因分布频率为T(70.1%)、C(29.9%),内异症组的基因型分布频率为TT(39.1%)、TC(46.3%)、CC(14.6%),等位基因分布频率为T(62.2%)、C(37.8%),差异无显著性(P>0.05);在汉族正常对照组基因型分布频率为TT(41.9%)、TC(46.7%)、CC(11.4%),等位基因分布频率为T(65.2%)、C(34.8%),内异症组基因型分布频率为TT(42.5%)、TC(51.2%)、CC(6.3%),等位基因分布频率为T(68.1%)、C(31.9%),差异无显著性。两个民族对照组之间与内异症组之间基因型频率与等位基因频率比较差异无显著性。在CYP1A1/MspI合并GSTM1(/)基因型的人群中,维吾尔族对照组与内异症组的基因型频率与等位基因频率分布比较均有显著差异(P<0.05),其TC+CC与TT比较,OR值为3.556(P<0.05)。汉族对照组与内异症组的比较无统计学差异。结论:解毒酶CYP1A1基因MspI多态性本身可能与维吾尔族及汉族内异症发病无关,而CYP1A1/MspI合并GSTM1(/)基因型可能与维吾尔族内异症发病有关。     

雌激素代谢酶CYP1A1及COMT基因多态性与子宫肌瘤相关性研究

目的:探讨雌激素代谢酶CYP1A1和COMT基因多态性与子宫肌瘤发生的关系。方法:应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术,对100例子宫肌瘤患者和100例对照组人群CYP1A1基因Msp I位点多态和COMT基因外显子4密码子158(G-A)多态性进行分析。结果:1两组均存在CYP1A1基因Msp I位点多态,但两组基因型TT、TC、CC频率和等位基因T、C频率的比较差异均无统计学意义(P0.05);2两组均存在COMT基因G-A多态,但两组基因型GG、GA、AA频率和等位基因G、A频率的比较差异均无统计学意义(P0.05)。结论:CYP1A1基因Msp I位点多态性和COMT基因外显子4密码子158(G-A)多态性与子宫肌瘤发病风险无相关性。     

CYP1A1基因多态性与子宫内膜腺癌发生的关系研究

目的研究细胞色素P4501A1(CYP1A1)基因MspI位点和Ile-Val位点多态性与子宫内膜腺癌发生的关系。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(PCR-RFLP)方法和等位基因特异性PCR(AS-PCR)技术检测84例子宫内膜腺癌患者和66例对照者CYP1A1基因MspI位点和Ile-Val位点的多态性。结果Ile-Val三种多态基因型在对照组和子宫内膜腺癌组中的分布在显著性差异(P<0.05),其中Ile/Val和Val/Val基因型在子宫内膜腺癌组中的分布频率明显高于对照组。与Ile/Ile基因型相比,Ile/Val基因型个体发生子宫内膜腺癌的相对危险度(OR)是2.682,两者差异有统计学意义(P<0.05);而MspI位点的多态性在对照组和子宫内膜腺癌组中的分布差异无统计学意义(P>0.05)。结论CYP1A1基因第7外显子的Ile/Val基因型与子宫内膜腺癌的发生有关,可以作为子宫内膜腺癌易感人群筛查的重要指标,MspI位点多态性与子宫内膜腺癌的发生无相关性。     

雌激素代谢基因CYP1A2和COMT单核苷酸多态性与妊娠期肝内胆汁淤积症关系的研究

目的:探讨参与雌激素代谢的CYP1A2和COMT基因多态性与成都地区妊娠期肝内胆汁淤积症(ICP)的关系。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,对成都地区100例ICP患者(ICP组)和100例正常孕妇(对照组)的CYP1A2基因5-'侧翼区G-2964A多态和COMT基因第4外显子第158号密码子G→A点突变所引起的缬氨酸→蛋氨酸(Val 158 Met)的错义突变多态进行分析。结果:CYP1A2 GA杂合基因型明显增加ICP的发病风险(P=0.029,OR=1.896),COMT含V等位基因的VV和VM基因型也明显增加ICP的发病风险(P=0.027,OR=3.996);两基因组合分析表明同时具有CYP1A2等位基因G和COMT等位基因V的个体发生ICP的风险显著增加(P=0.011,OR=2.852)。结论:CYP1A2和COMT基因单核苷酸多态性与成都地区ICP的易感性有关。     

CYP1A1基因MspⅠ位点多态性与子宫肌瘤易感性的研究

目的:探讨细胞色素P450(cytochrome P450,CYP)1A1基因MspⅠ位点多态性与鲁北地区汉族女性子宫肌瘤的关系。方法:以病例-对照的研究方法,采用PCR-RFLP方法检测了123例子宫肌瘤患者和123例匹配对照者的CYP1A1基因MspⅠ位点的基因多态性。应用Logistic回归等方法分析基因多态性与子宫肌瘤的关系。结果:(1)CYP1A1基因MspⅠ位点的基因型在子宫肌瘤组与对照组中分布的差异无统计学意义(P=0.927);(2)杂合型(T/C)和突变型(C/C)与野生型(T/T)在子宫肌瘤组与对照组的分布差异均无统计学意义(P=0.738,P=0.947);(3)合并杂合型(T/C)和突变型(C/C)与野生型(T/T)比较,在子宫肌瘤组与对照组分布的差异无统计学意义(P=0.925)。结论:CYP1A1MspⅠ等位基因多态性与鲁北地区汉族女性子宫肌瘤的易感性无显著相关性。     

CYP1A1基因MspI位点和SULT1A1基因Arg213His位点多态性与子宫肌瘤的关联性研究

目的 探讨细胞色素P450 (cytochrome P450, CYP)1A1 基因MspⅠ位点和硫酸氨基转移酶(sulfotransferase, SULT) 1A1 基因 Arg213His位点多态性与鲁北地区汉族女性子宫肌瘤的关系。 方法 采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测123例子宫肌瘤患者和123例健康对照组的CYP1A1 基因 MspⅠ位点的基因型和SULT1A1 基因 Arg213His位点的基因型,分析基因多态性与子宫肌瘤的关系。 结果 子宫肌瘤组CYP1A1基因MspⅠ位点的基因型与对照组中的分布比较,差异无统计学意义(P=0.927); 而子宫肌瘤组SULT1A1 基因Arg213His位点的基因型与对照组中的分布比较,差异有统计学意义( P=0.011)。CYP1A1基因MspI位点和SULT1A1基因Arg213His位点多态性在子宫肌瘤的发生过程中的交互作用比较,差异有统计学意义( P=0.024 )。 结论 CYP1A1 基因MspⅠ位点多态性与鲁北地区汉族女性子宫肌瘤的易感性无显著相关;SULT1A1 基因Arg213His位点多态性与鲁北地区汉族女性子宫肌瘤的发生有关,并增加了子宫肌瘤的患病风险;CYP1A1基因MspI位点和SULT1A1基因Arg213His位点多态性在子宫肌瘤的发生过程中具有交互作用。     

CYP1A1基因MspⅠ位点和SULT1A1基因Arg213His位点多态性与子宫肌瘤的关联性研究

目的 探讨细胞色素P450(cytochrome P450,CYP)1A1基因MspⅠ位点和硫酸氨基转移酶(sulfotransferase,SULT)1A1基因Arg213His位点多态性与鲁北地区汉族女性子宫肌瘤的关系.方法 采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测123例子宫肌瘤患者和123例健康对照组的CYP1A1基因MspⅠ位点的基因型和SULT1A1基因Arg213His位点的基因型,分析基因多态性与子宫肌瘤的关系.结果 子宫肌瘤组CYP1A1基因MspⅠ位点的基因型与对照组中的分布比较,差异无统计学意义(P=0.927);而子宫肌瘤组SULT1A1基因Arg213His位点的基因型与对照组中的分布比较,差异有统计学意义(P=0.011).CYP1A1基因MspⅠ位点和SULT1A1基因Arg213His位点多态性在子宫肌瘤的发生过程中的交互作用比较,差异有统计学意义(P=0.024).结论 CYP1A1基因MspⅠ位点多态性与鲁北地区汉族女性子宫肌瘤的易感性无显著相关;SULT1A1基因Arg213His位点多态性与鲁北地区汉族女性子宫肌瘤的发生有关,并增加了子宫肌瘤的患病风险;CYP1A1基因MspⅠ位点和SULT1A1基因Arg213His位点多态性在子宫肌瘤的发生过程中具有交互作用.     

细胞色素P450基因多态性与妇科肿瘤易感性

细胞色素P450(CYP)是微粒体混合功能氧化酶中最重要的一族氧化酶，在生物体内分布广泛，CYP参与多种外源性化合物的代谢及内源性物质的生成同种CYP在人群中可以表现为不同表型，这种遗传多态现象决定了CYP对特定的外来化合物及内源性物质在反应上的差异，即表现为个体对致癌物的不同易感性。就近年来CYP基因、基因多态性的研究现状及CYP1A1、CYP1B1、CYP17和CYP19的多态性与妇科肿瘤易感性的研究进展综述。     

醛固酮合成酶基因多态性与多囊卵巢综合征相关性的研究

目的　探讨醛固酮合成酶 (CYP11B2 )基因多态性与多囊卵巢综合征 (PCOS)发病的关系。方法　采用聚合酶链反应、限制性内切酶消化及电泳技术 ,对 92例PCOS患者和 60例正常妇女的CYP11B2基因 3 44T位点基因多态性进行检测 ,并测定基础状态下促卵泡激素、促黄体生成素、雌二醇、睾酮、孕酮、泌乳素、血肾素活性、血管紧张素Ⅱ及醛固酮水平 ,比较不同基因型PCOS患者及正常妇女的肾素、血管紧张素、醛固酮及雄激素水平差异。结果　 ( 1)正常妇女、PCOS患者中 ,CYP11B2基因 3 44T位点C基因频率分别为 2 2 %和 3 6%。 ( 2 )PCOS患者T→C(TC、CC)出现率为 5 7% ,明显高于正常妇女的 3 7% (P <0 0 5 )。 ( 3 )PCOS患者CYP11B2基因型及基因频率的分布与正常妇女比较 ,差异有显著性 (P <0 0 5 ) ;CYP11B2基因 3 44TC、 3 44CC基因型的PCOS患者及正常妇女的肾素、血管紧张素、醛固酮及雄激素水平 ,均明显高于CYP11B2基因 3 44TT基因型者 (P <0 0 1)。结论　 ( 1)CYP11B2基因 3 44T位点变异 (T→C)的出现 ,可能增大了患PCOS的风险 ,并与PCOS发病有关。 ( 2 )CYP11B2基因 3 44CC、 3 44TC基因型可能是PCOS的易患基因型 ,并与PCOS患者肾素血管紧张素系统功能亢进有一定的关系     

ET-1、ETA-R在宫颈癌中的表达与HPV感染的关系

目的:探讨ET-1及ETA-R表达在宫颈癌发生中的病理生理作用及其与HPV感染的关系。方法:应用免疫组化SP法对68例宫颈癌组织及10例非癌变宫颈组织进行ET-1、ETA-R、HPV16/18E6免疫特异性染色。结果:(1)HPV16/18E6阳性率在宫颈癌中占82.3%,对照组宫颈组织中占20%,二组HPV16/18E6表达有统计学差异(P<0.001);(2)HPV阳性宫颈癌组织ET-1、ETA-R阳性表达率100%,而HPV阴性宫颈癌组织ET-1、ETA-R阳性表达率0%,对照组ET-1、ETA-R阳性表达率20%,3组ET-1、ETA-R表达有统计学差异(P<0.001);(3)ET-1、ETA-R在宫颈癌中的表达均与临床分期、病理分级、组织学类型无关(P>0.05)。结论:HPV是否感染与功能性ET-1/ETA-R自分泌环有关,而ET-1/ETA-R自分泌环是肿瘤生长的驱动器,其功能上调可能是HPV感染子宫颈上皮细胞引起宫颈癌发生的一种新的调控机制。     

The relationship between single nucleotide polymorphisms in estrogen-metabolizing genes CYP1A1,CYP17,COMT and estrogen receptor alpha and the risk of endometrial adenocarcinoma among the Chinese women

<正>Objective:To explore whether polymorphisms of the genes responsible for catechol estrogen(CE)formation via estrogen biosynthesis(CYP17)and hydroxylation (CYP1A1)and CE inactivation(COMT)and ERa are associated with an elevated risk for en- dometrial adenocarcinoma in Chinese women.Methods:A multigenic case-control study was conducted,eighty-seven endometrial adenocarcinoma patients and ninety controls were recrui- ted.PCR-RFLP assays were used to determine the genotypes of estrogen-metabolizing genes and ERa gene.Results:The endometrial adenocarcinoma risk associated with individual susceptibili- ty genotypes varied among the six polymorphic sites and was the highest for CYP17,followed by CYP1 A1 Ile-Val,CYP1A1 MspI,COMT,ERa XhaI and ERa PvuII.Multivariate logistic regres- sion showed the CYP1A1 MspI genotype was the most significant determinant for endometrial adenocarcinoma development and was associated with a 3.61 fold increase in risk(95% confi- dence interval,1.73～7.55).Furthermore,a trend of increasing risk for developing endometrial adenocarcinoma was found in women harboring higher numbers of high-risk genotypes.Conclu- sion:The CYP1A1,CYP17 and ERa XbaI genotypes are related to the susceptibility of endome- trial adenocarcinoma,they may be useful markers for predicting endometrial adenocarcinoma susceptibility.The allele encoding for low acticity COMT,ERa PvuII may not be a genetic risk factor for endometrial adenocarcinoma.     

CYP1A1 and CYP1B1 genetic polymorphisms and uterine leiomyoma risk in Chinese women

Purpose  The aim of the study was to evaluate the association of CYP1A1 and CYP1B1 polymorphisms with uterine leiomyoma in Chinese women. Methods  We investigated 100 women with clinically diagnosed uterine leiomyoma and 110 healthy normal subjects from Chinese women. The genetic distribution of two CYP1A1 polymorphisms at MspI, Ile462Val and four CYP1B1 polymorphisms at Arg48Gly, Ala119Ser, Leu432Val, Asp449Asp were analyzed by polymerase chain reaction–restriction fragment length polymorphism and DNA sequencing method. Results  All the SNPs showed polymorphisms in Chinese women. The genotype A/G and the allele G on Ile462Val was significantly different between uterine leiomyoma patients and controls (P < 0.05). Conclusion  These results suggest that the genotype of CYP1A1 Ile462Val was associated with the increased risk of uterine leiomyomas in Chinese women. Capsule This is the first report that demonstrates the polymorphism at Ile462Val of CYP1A1 to be associated with uterine leiomyoma in Chinese women.     

CYP1B1基因多态性与卵巢癌易感性的研究

目的:研究CYP1B1基因外显子2密码子119(G-T)、外显子3密码子432(C-G)多态性与卵巢癌遗传易感性的关系。方法:应用等位基因特异性聚合酶链反应(AS-PCR)法对53例卵巢癌患者和30例对照者进行CYP1B1基因密码子119(G-T)、密码子432(C-G)突变分析,用免疫组化SP法进一步研究雌激素受体(ER)、孕激素受体(PR)的表达,分析其是否受CYP1B1基因多态性的影响。结果:CYP1B1基因密码子432中等位基因C、G在卵巢癌组和对照组分布的差异有统计学意义(P<0.05),其中等位基因G使卵巢癌发病风险增加2.71倍。CYP1B1基因密码子432C/G各基因型分布两组间差异有统计学意义(P<0.01),纯合突变(G/G)基因型、杂合突变(C/G)基因型与野生(C/C)基因型相比,患卵巢癌的危险度分别提高了4.53倍和4.43倍。此外,432G/G、C/G基因型者ER阳性表达率高于432(C/C)基因型,三者间有显著差异(P<0.05)。结论:CYP1B1基因密码子432突变等位基因与卵巢癌的发生有一定关系,突变基因型增加了卵巢癌的发病风险,且与ER的表达相关。     

CYP1A1 gene polymorphism and risk of endometrial hyperplasia and endometrial carcinoma

The cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens and estrogen. We hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for endometrial hyperplasia (EH) and endometrial carcinoma (ECa). We therefore evaluated this hypothesis in patients with EH and ECa and control subjects using allele-specific polymerase chain reaction-based method in a Turkish population. The patients with CYP1A1 Ile/Val genotype had a fivefold higher risk of having EH than those with Ile/Ile. In contrast, a higher frequency of any Val genotype (Ile/Val and Val/Val) was found in patients with EH, indicating that persons carrying any Val allele are at increased risk for developing EH. In the ECa group, patients were also more likely to have CYP1A1 Ile/Val allele, with an adjusted odds ratio of 3.0. Moreover, there was a statistically significant increase in relative risk association with any Val genotype between patients and controls, suggesting that individuals carrying any Val genotype are at increased risk for developing ECa. We concluded that variant alleles of the CYP1A1 gene might be associated with EH and ECa susceptibility. Further studies with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.     

CYP1A1 gene polymorphism as a risk factor for cervical intraepithelial neoplasia and invasive cervical cancer

OBJECTIVE: The purpose of this study was to evaluate the role of CYP1A1*3 gene polymorphism in the development of cervical cancer by comparing patients having cervical intraepithelial neoplasia (CIN) or invasive cervical cancer with control subjects. METHODS: CYP1A1*3 polymorphism was analyzed using an allele-specific PCR-based method. RESULTS: In the group of patients with CIN, the frequency of the Ile/Val and of any Val alleles was significantly higher than in the healthy control subjects (OR: 4.51; 95%CI = 2.42-8.43, and OR: 3.71; 95%CI = 2.03-6.78). In the CIN1 group, patients with Ile/Val and any Val genotypes were found to be significantly higher (OR: 10.53; 95%CI = 3.78-29.33 and OR: 8.38; 95%CI = 3.04-23.08). In the CIN2 group, patients with Ile/Val and any Val revealed a 4.06- and 3.23-fold higher risk than those with Ile/Ile (95%CI = 1.54-10.74 and 1.24-8.45). However, the variance in the group of patients with CIN3 did not reach statistical significance. Patients with cervical cancer were analyzed with respect to the histological diagnoses. In the adenocancer group, the estimated ORs with respect to the control subjects were 11.29 for Ile/Val (95%CI = 3.35-38.07) and 8.98 for any Val groups (95%CI = 2.69-30.01), with a statistical significance. Among the squamous cell cancer patients, Ile/Val and any Val were significantly higher than in controls (OR: 5.76; 95%CI = 3.13-10.59 and OR: 5.20; 95%CI = 2.91-9.28). Although Val/Val genotype did not reach a significant value, it was near significance with an OR of 3.03 (95%CI = 0.95-9.68). CONCLUSION: These results suggest that CYP1A1*3 gene polymorphism is linked to a propensity for cervical carcinogenesis and further series are needed to detect the exact role of this unique variation.     

Association of CYP1A1 and CYP1B1 polymorphisms with bone mineral density variations in postmenopausal Mexican-Mestizo women

Herein, we investigated potential associations between polymorphisms of genes related to estrogen metabolism and bone mineral density (BMD) in postmenopausal women. This was a cross-sectional study, in which two hundred and ninety postmenopausal Mexican-Mestizo women were studied. The BMD of the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured. The distribution of the genetic polymorphisms, including rs1799814 and rs1048943 at CYP1A1 as well as rs1056836 at CYP1B1, were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP), single-stranded conformational polymorphism (SSCP), and DNA sequencing. Deviations from Hardy–Weinberg equilibrium (HWE) were tested, and linkage disequilibrium (LD) was calculated by direct correlation (r²). Moreover, haplotype analysis was performed. All polymorphisms were in HWE. The genotype and allele distributions of the three single nucleotide polymorphisms (SNPs) studied showed no significant differences. However, statistical significance was reached when constructing haplotypes. The CG haplotype in CYP1A1 was associated with variations in LS and FN BMD after adjustment for covariates (p?=?0.021 and 0.045, respectively), but the association with TH BMD was not significant. These results suggested that the CG haplotype in CYP1A1 may play an important role in the mechanism of osteoporosis and may be useful as a genetic marker.