CYP2E1和GSTM1多态性与再生障碍性贫血遗传易感性研究

目的探讨CYP2E1和GSTM1基因多态性与再生障碍性贫血（简称再障）遗传易感性的关系。方法采用聚合酶链反应（PCR）和PCR—限制性片段长度多态性方法（PCR-RFLP）分别研究104例再障患者和110名健康对照的GSTM1和CYP2E1的PstⅠ基因型。结果CYP2E1（c1c2,c2c2）基因型在再障组和对照组的频率分别为49.04%、46.36%,差异无统计学意义（P〉0.05）;GSTM1（-）基因型在再障组和对照组的频率分别为75.96%、48.18%,差异有统计学意义（P〈0.05）,联合分析时发现,CYP2E1（c1c2,c2c2）＋GSTM1（-）基因型的个体患再障危险性升高[比值比（OR）=10.56,95%可信区间（CI）=4.34-22.87];工作和生活环境质量较差和饮酒是再障发生的危险因素。结论CYP2E1（c1c2,c2c2）＋GSTM1（-）基因型可能是再障遗传易感性标志物,携带该基因型的个体患再障的危险性高于其他基因型。     

CYP2E1和GSTM1多态性与再生障碍性贫血遗传易感性研究

目的探讨CYP2E1和GSTM1基因多态性与再生障碍性贫血(简称再障)遗传易感性的关系。方法采用聚合酶链反应(PCR)和PCR—限制性片段长度多态性方法(PCR-RFLP)分别研究104例再障患者和110名健康对照的GSTM1和CYP2E1的PstⅠ基因型。结果CYP2E1(c1c2,c2c2)基因型在再障组和对照组的频率分别为49.04%、46.36%,差异无统计学意义(P>0.05);GSTM1(-)基因型在再障组和对照组的频率分别为75.96%、48.18%,差异有统计学意义(P<0.05),联合分析时发现,CYP2E1(c1c2,c2c2) GSTM1(-)基因型的个体患再障危险性升高[比值比(OR)=10.56,95%可信区间(CI)=4.34~22.87];工作和生活环境质量较差和饮酒是再障发生的危险因素。结论CYP2E1(c1c2,c2c2) GSTM1(-)基因型可能是再障遗传易感性标志物,携带该基因型的个体患再障的危险性高于其他基因型。     

CYP2E1基因多态性与宣威肺癌易感性的病例对照研究

目的 探讨宣威地区CYP2E1基因多态性与肺癌易感性的关系.方法 采用聚合酶链式反应(PCR) 和限制性片段长度多态性(RFLP) 技术检测108例宣威肺癌患者和108例对照的RsaI识别的CYP 2E1基因型CYP2E1的基因多态性.结果 此次研究结果为CYP 2E1基因型频率在肺癌组和对照组的分布差异无统计学显著性意义(χ2=1.571,P＞0.05);烧烟煤者发生肺癌的危险性升高(OR=2.473,P＜0.05),CYP 2E1C1/C1基因型且烧烟煤者患肺癌的风险明显增高(OR=3.492,P＜0.05);饮酒与肺癌风险有较强的联系(OR=3.654,P＜0.05),CYP2E1C1/C1基因型且饮酒者患肺癌的风险明显增高(OR=5.7,P＜0.05) .结论 CYP 2E1基因多态性与肺癌无明显相关性,但与烧烟煤及饮酒有联合作用.     

儿童急性白血病GSTM1、GSTF1基因多态性分析

谷胱甘肽S-转移酶超家家族（GSTs）参与致突变物在体内的代谢解毒过程。其中的GSTM1（编码μ），GSTT1(编码θ）基因在人群中呈多态性分布。已证实GSTM1、GSTT1基因多态性与多种恶性肿瘤的易感性有关。我们就GSTM1、GSTT1基因多态性与儿童急性白血病易感性的关系进行研究。     

深圳地区汉族急性白血病儿童GSTP1全编码区基因多态性分析

目的研究深圳地区汉族急性白血病(AL)患儿谷胱甘肽转移酶P1(GSTP1)基因全编码区内的单核苷酸多态性(SNPs)基因型和等位基因频率分布特征。方法用RT-PCR和变性梯度凝胶电泳(DGGE)技术对108例AL患儿和121例对照儿童的GSTP1全编码区内的SNPs进行筛查分析。结果在GSTP1全编码区内共筛查到3个SNPs位点,包括1个热点突变位点A313G(Ile105Val,rs1695)、1个错义突变位点G439T(Asp147Tyr,rs4986949)和1个同义突变位点T555C(Ser185Ser,rs4891),其在汉族儿童分布等位基因总频率分别为16.4%、1.3%和16.4%,且具有明显的种族差异性。GSTP1 A313G、G439T和T555C多态性各基因型和等位基因频率分布在AL患儿和对照组儿童中差异均无统计学意义(P分别为0.691和0.359;0.898和0.581、0.691和0.359)。结论对深圳地区汉族儿童GSTP1基因全编码区多态性进行筛查分析,确定了GSTP1 A313G,G439T和T555C 3个SNPs位点,其具有种族差异性且与儿童AL发病风险均无关。     

谷胱甘肽S 转移酶M1和T1基因多态性与鼻咽癌遗传易感性的Meta分析

鼻咽癌（NPC）是恶性程度较高的肿瘤,EB病毒与NPC的发生密切相关,且受遗传、环境、饮食等因素影响［1,2］,谷胱甘肽-S-转移酶M1（GSTM 1）、谷胱甘肽-S-转移酶T1（GSTT 1）、细胞色素P450、HLA I型和II型的突变可以增加NPC的发病风险［3］。GSTT 1和GSTM 1为谷胱甘肽硫转移酶（GST）超基因家族中的成员,参与机体毒物代谢和解毒,属于II相代谢酶,基因多态性表现为GST酶活性的升高或降低进而影响机体对毒物和致癌物易感性的改变［4,5］。目前探讨GSTT 1、GSTM 1基因多态性与NPC的文献不少,但因样本量小、地区差异、肿瘤部位、遗传、饮食和环境等因素的交互作用导致研究结果存有争议。本文对已发表的文献进行Meta分析,以寻找NPC特异性的筛查、诊断指标。     

GSTM1、GSTT1基因多态性与儿童急性髓细胞性白血病易感性的相关研究

目的　研究GSTM 1、GSTT1基因多态性与儿童急性髓细胞性白血病 (AML)易感性的相关关系。方法　对 4 9例AML患儿和 14 6名健康人的GSTM 1、GSTT1基因型进行分析。结果　AML患儿的GSTM 1基因纯合性缺失率显著高于对照组 (OR =2 .4 82 ,P <0 .0 5 )。但AML患儿的GSTT1基因纯合性缺失率、GSTM 1 T1基因纯合性联合缺失率与对照组间差异无显著性。结论　GSTM 1纯合性缺失基因型可能是儿童发生AML的危险基因型 ,而GSTT1纯合性缺失基因型可能与儿童AML易感性无关     

CYP3A4基因多态性与临床疾病易感性的研究进展

细胞色素P450 3A4(CYP3A4)作为人体内代谢药物的主要酶细胞色素P450超家族中的重要成员,参与多种内、外源性化学物质在人体内的转化代谢的过程,而其基因多态性也与多种临床疾病的易感性密切相关。本文就CYP3A4基因多态性与临床多种疾病的易感性作一综述。     

CYP1A1、NAT2基因多态与急性淋巴细胞白血病的关系

目的探讨CYP1A1MspI、NAT2基因多态与急性淋巴细胞白血病(ALL)易感性的关系。方法应用PCR-RFLP和自动实时荧光Light-cycler技术,分析78例ALL患者和112例健康人CYP1A1MspI和NAT24个位点基因多态性,比较ALL患者与对照组间频率差异。结果基因多态位点,各等位基因和基因型频率与对照组比较有显著性差异(p<0.05),其中等位基因m2使患ALL的危险度提高了1.54倍,m1m2、m2m2基因型使患ALL的危险度分别提高了2.27倍和2.77倍,ALL组NAT2慢乙酰化基因型频率与对照组比较有显著性差异(p<0.05);同时具有MspI和慢乙酰化基因型的个体ALL易患风险明显升高(p<0.01,OR=7.14)。结论CYP1A1MspI基因多态和NAT2慢乙酰化基因型可能与ALL的发生有关。     

CYP2E1 and GSTM1 gene polymorphisms,environmental factors,and the susceptibility to lung cancer

Objective

To investigate the relationships between the CYP2E1 RsaI polymorphism, GSTM1 polymorphism, and the susceptibility to lung cancer, along with the interactions between environmental factors and these genes.

Methods

A case‐control study was carried out to explore the independent effect of gene polymorphisms on risk of lung cancer, and the combined effects of gene loci. The stratification analysis of age, sex, smoking, and drinking combined with positive loci was also analyzed, and any interaction was identified.

Results

The logistic regression analysis showed that there were statistical relationships between the CYP2E1 RsaI TT genotype and lung cancer, GSTM1 (−) and lung cancer. The combined effect's analysis of these 2 loci showed that, with an increase in the number of risk alleles, the risk of lung cancer also increased (supposing 0 risk allele as the reference group). Subjects carrying 3 risk alleles had the highest risk of developing lung cancer with an adjusted OR = 10.38 (95% CI 2.10‐51.35). Stratified analysis showed that, in women, nonsmoking subjects, or nondrinking subjects, the combined effects could increase the risk of lung cancer; no heterogeneity was found between these layers except sex. The interaction analysis showed that, supposing the male, GSTM1 (+) genotype as the reference, the female, GSTM1 (−) genotype had a significantly increased risk of lung cancer (OR = 2.17 [1.01‐4.70]); when the non‐smoking, GSTM1 (+) genotype subjects was the reference group, smoking, GSTM1 (+) genotype subjects and smoking, GSTM1 (‐) genotype subjects had significantly higher risk of lung cancer (OR = 2.00 [1.01‐3.96], OR = 2.89 [1.28‐6.54]).

Conclusion

CYP2E1 RsaI TT genotype was a protective factor against the development of lung cancer, while GSTM1 (−) genotype was a risk factor for lung cancer. Increases in the number of the risk alleles also increased lung cancer risk. GSTM1 (−) genotype, sex, and smoking status might interact in the incidence of lung cancer.

     

CYP2B6基因多态性与成年人急性髓系白血病易感性的相关性

目的 探讨CYP2B6基因多态性与成年人急性髓系白血病(AML)易感性的相关性.方法 选取87例首次确诊AML的患者作为AML组,191例健康体检者作为对照组,运用Sanger测序法对CYP2B6785A>G与516G>T两个单核苷酸多态性位点进行基因分型.结果 CYP2B6785A>G位点在显性模型下(AG+GG v...     

CYP2C19基因多态性检测的临床实验室性能验证

目的对人细胞色素P450酶等位基因(CYP2C19)多态性检测试剂盒进行性能验证。方法根据中国合格评定国家认可委员会CNAS-GL039:2019《分子诊断检验程序性能验证指南》相关要求,结合试剂盒说明书,从符合率、精密度、检出限和抗干扰能力4个方面对“人CYP2C19基因多态性检测试剂盒(荧光PCR法)”进行性能验证。符合率验证采用荧光PCR法和Sanger测序法检测;精密度验证选择杂合突变CYP2C19 c.681GA、c.636GA样本进行检测;抗干扰能力验证判断基因型检测是否受影响。结果PCR法和Sanger测序法的检测符合率为100%;CYP2C19 c.681 G和A等位基因的FAM和ROX荧光通道精密度检测CV值分别为3.78%、1.76%、3.76%和3.56%;CYP2C19 c.636 G和A等位基因的FAM和ROX荧光通道精密度检测CV值分别为3.08%、2.81%、3.40%和3.73%;样本最低检出限为10 ng/μL;抗干扰能力验证显示基因型可以正常检测。结论人CYP2C19基因多态性检测试剂盒(荧光PCR法)符合ISO15189质量管理要求,可以为临床提供准确可靠的检测结果。     

沈阳汉族人群细胞色素P450 酶1A2基因多态性与慢性阻塞性肺疾病易感性的关联

目的探讨沈阳市汉族人群细胞色素P450 酶1A2 (CYP1A2)基因多态性与慢性阻塞性肺疾病(COPD)遗传易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RELP)方法检测100 例COPD患者和年龄、性别匹配的100 名健康人CYP1A2 基因不同位点多态性等位基因及基因型频率分布。结果两组不同位点多态性基因型频率分布均符合遗传性Hardy-Weinberg平衡(均P>0.05)。COPD患者和健康人的1D和1F基因型和等位基因频率分布有显著性差异(P<0.05),1C和1E基因型和等位基因频率分布无显著性差异(P>0.05)。结论CYP1A2 基因1D和1F多态性可能与COPD遗传易感性增加有关。     

GSTM1、GSTT1基因多态性与白血病易感性的分析

目的分析GSTM1缺失基因型与白血病遗传易感性的关系。方法 131例白血病患者纳入病例组,200例体检健康者纳入对照组。采用巢式PCR检测GSTM1、GSTT1基因型。应用χ2检验和精确概率法比较各基因型频率在病例组与对照组之间的差异,用比值比(OR)及其95%的可信区间(CI)表示各基因型发生白血病的风险度。结果病例组GSTM1缺失基因型频率与对照组比较,差异有统计学意义(P=0.000 1,其OR值为2.152,95%CI为2.301~5.985);在病例组与对照组中均未检测到GSTT1缺失基因型;CML、AML与ALL组间进行GSTM1缺失基因型频率比较,差异无统计学意义(P0.05)。结论GSTM1缺失基因型可能是白血病的重要危险因素。     

急性脑梗死患者CYP2C19基因多态性与纤维蛋白原及D-二聚体相关性研究

目的 探讨急性脑梗死患者细胞色素P450酶等位基因(CYP2C19基因)多态性与纤维蛋白原(FIB)及D-二聚体相关性.方法 选取常规服用氯吡格雷超过1个月的急性脑梗死患者112例为研究对象,采用RT-PCR法检测脑梗死患者外周全血CYP2C19基因型,运用凝固法(Clauss法)检测FIB,透射比浊法检测血浆中D-二...     

Assessment of CYP2C19 genetic polymorphisms in a Korean population using a simultaneous multiplex pyrosequencing method to simultaneously detect the CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles

Background and objective: CYP2C19 is a drug‐metabolizing enzyme showing various genetic polymorphisms that may cause marked interindividual and interethnic variability in the disposition of its substrates. We assessed CYP2C19 genetic polymorphisms in a Korean population using a newly developed multiplex pyrosequencing method. Method: A multiplex pyrosequencing method to simultaneously detect CYP2C19*2, *3, and *17 alleles was designed. We established the frequency of these CYP2C19 alleles in 271 Korean subjects using the multiplex pyrosequencing method. Results: The results showed 100% concordance between single and multiplex pyrosequencing methods. We also validated the polymorphisms identified by pyrosequencing with direct sequencing method. The allele frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 were 0·284, 0·101 and 0·015 respectively. These frequencies are similar to that reported for other Asian populations including Japanese and Chinese but different from that of Caucasians and Africans. Conclusions: The multiplex pyrosequencing method to detect CYP2C19*2, CYP2C19*3, and CYP2C19*17 concurrently, seems to be a rapid and reliable genotyping method for the detection of important CYP2C19 genetic polymorphisms. Similar to studies conducted on other Asian populations, this study reported that in the Korean population tested, the CYP2C19*2 and CYP2C19*3 alleles were relatively frequently found, whereas the frequency of CYP2C19*17 was very low.     

Cytochrome P450 2E1 activity in diabetic and obese patients as assessed by chlorzoxazone hydroxylation

Summary— Cytochrome P450 2E1 (CYP2E1) is a phase I detoxification enzyme, which is induced by chronic alcohol consumption. It is involved in the activation of numerous carcinogens and in the production of free radicals. As it has previously been shown to be induced in diabetic and obese rats, the aim of this study was to investigate its induction level in poorly-controlled diabetics and in obese patients (Body Mass Index > 30 kg/m²). CYP2E1 activity was determined in 35 diabetic and 17 obese patients by using the in vivo chlorzoxazone hydroxylation test. Even though the glucidic parameters were highly disturbed (mean fasting glycemia > 7.9 mmol/L, post prandial glycemia > 12.2 mmol/L and fructosamine > 326 μmol/L), CYP2E1 activity was not enhanced either in insulin-dependent diabetics (IDDs, n = 7) nor in non-obese non-insulin-dependent diabetics (NTTDDs, n = 15) when compared to controls ( n = 42) (0.21 ± 0.03, 0.33 ± 0.03 and 0.30 ± 0.02, respectively, mean ± SEM). However, this activity was lower in IDDs when compared to NIDDs ( P < 0.05). In obese patients, with ( n = 13) or without ( n = 17) NIDD mellitus, CYP2E1 activity was increased by a mean of 40% when compared to controls. In addition, positive correlations were found in all subjects (controls or patients, n = 74) between CYP2E1 activity and serum cholesterol ( r = 0.42, P < 0.0001), triglycerides ( r = 0.44, P < 0.0001) and BMI ( r = 0.36, P < 0.001). Accordingly, subjects with cholesterol and/or triglyceride serum levels above 6.4 and 1.8 mmol/L, respectively, displayed a mean increase of 40% of their CYP2E1 activity vs subjects within the above values. It is believed that individuals with increased CYP2E1 activity are more susceptible to the adverse effects of CYP2E1-mediated activation of toxins and carcinogens.