CYP2J2基因和EPHX2基因多态性与缺血性脑卒中的遗传易感性

目的 研究我国汉族人群细胞色素P450表氧化酶2J2(CYP2J2),可溶性环氧化物水解酶2(EPHX2)基因多态性与缺血性脑卒中的关系.方法 选择200例缺血性脑卒中患者和350例健康人群,采用PCR-RFLP技术分析两个基因CYP2J2 G-50T,EPHX2 G860A多态性的基因型.结果 仅EPHX2 860A等位基因频率在缺血性脑卒中组与对照组比较有显著性差异.多元Logistic回归分析表明,携带EPHX2 860A等位基因的人群患缺血性脑卒中相对风险率下降50%(OR=0.5).当个体同时携带CYP2J2-50GG和EPHX2 860A (A 示A等位基因)联合基因型时,其患缺血性脑卒中相对风险率下降53.9%(OR=0.461).结论 虽然EPHX2 860A等位基因与缺血性脑卒中有相关性并且为缺血性脑卒中一个独立的保护因子,但联合基因型CYP2J2-50GG/EPHX2 860A 的协同作用对缺血性脑卒中有更强的保护作用.     

FOXC2基因C-512T和G-350T多态性与2型糖尿病相关性的初步分析

目的探讨叉头框c2（FOXC2）基因5qE翻译区c-512T和G-350T多态性与2型糖尿病（T2DM）的相关性。方法选择云南省汉族人群280例,其中T2DM患者159例为T2DM组,无糖尿病家族史的健康对照121名为对照（Nc）组。应用PCR—RFLP检测FOXC2基因5q#翻译区c-512T和G-350T多态性。结果T2DM组和NC组组间,FOXC2基因C-512T和G-350T的基因型和等位基因频率分布差异均无统计学意义,且与性别无关。T2DM组-12C／C基因型携带者具有更高的wHR（P％O．05）,该人群患脂肪肝的比例明显升高（P〈0．05）。-350G／G基因型携带者具有更高的HDL—C（P〈0．05）,该人群患脂肪肝的比例明显降低（P〈0．01）。结论T2DM患者FOXC2基因C-512T多态性与wHR、脂肪肝相关;G-350T多态性与HDLC、脂肪肝相关。     

抵抗素基因+299G/A多态性与T2DM并高血压病的相关性

目的研究抵抗素基因＋299G／A多态性与中国北方地区汉族人群2型糖尿病（T2DM）并高血压病的关系。方法采用聚合酶链式反应-限制性片段长度多态性技术检测北方地区汉族人群261例T2DM患者的抵抗素基因内含子2区299G／A突变。结果T2DM组GG、GA、AA基因型及G／A等位基因频率与非T2DM组比较有显著统计学差异（P〈0．01）；T2DM组GG基因型携带者空腹血糖明显高于AA基因型携带者（P〈0．05）。多元线性逐步回归分析显示，抵抗素基因＋299G／A与收缩压、舒张压无明显相关性。结论抵抗素基因＋299G／A多态性与T2DM有关．与高血压病元明显相关性。     

2型糖尿病人群CDKN2A／B基因多态性与冠心病风险的相关性研究

目的观察T2DM人群细胞周期蛋白依赖激酶抑制基因2A／B（CDKN2A／B）基因多态性是否与冠心病风险相关,以早期筛查DM人群中冠心病的高危人群。方法对我院因胸痛症状行冠脉造影或冠脉CT检查的T2DM患者,根据冠脉造影或冠脉CT结果分为冠心病组及非冠心病组。冠心病组共220例,非冠心病组共89例。根据Hapmap数据库选取CDKN2A／B共7个单倍型标记的单核苷酸多态性（SNP）：CDKN2Ars2811708（G〉T）、rs3088440（A〉G）和rs3731239（C〉T）,CDKN2Brs3217986（A〉C）、rs1063192（C〉T）、rs2285327（A〉G）和rs3217992（A〉G）。对所有个体进行PCR扩增并通过RFLP或基因测序方法读取个体的基因型。结果在T2DM人群中,冠心病组中cDKN2Ars2811708的次要等位基因T频率（26．4％）显著高于非冠心病组（17．4％）（P〈0．05）,基因型分布在两组问存在显著性差异（P〈0．05）,G／T基因型携带者较G／G基因型携带者发生冠心病的风险显著增加（P（0．05）,在校正心血管其他风险因素（如性别、年龄、BMI、DM病程、高血压病病史、脂代谢异常病史、吸烟史）后,这种相关性仍然存在（P〈0．01）。结论T2DM人群中,CDKN2A／B基因单核苷酸多态性可能与冠心病的风险相关。     

色素上皮衍生因子启动子区基因多态性与糖尿病微血管病变的关系

目的观察色素上皮衍生因子（PEDF）启动子区单核苷酸多态性（SNP）与糖尿病微血管病变的关系。方法将271例T2DM患者分为无糖尿病微血管病变组105例,合并糖尿病微血管并发症组166例,分析PEDF基因启动子区rs12150053T／C及rs12948385G／A的基因型和等位基因频率。结果两个SNPs位点等位基因频率均有统计学差异（P〈0．05）,rs12948385位点基因型频率也有统计学差异（P〈0．05）。结论PEDF启动子区多态性位点可能是我国北方汉族人群糖尿病微血管病变发病的危险因素之一。     

单核细胞趋化蛋白-2518G/A基因多态性与冠心病的关系

目的研究单核细胞趋化蛋白-1（MCP-1）-2518G／A基因多态性对冠心病发病的影响。方法选取冠心病患者300例,正常对照组60例。冠心病患者分急性冠状脉综合征（ACS）组180例以及稳定型心绞痛（SAP）组120例。所有患者行冠状动脉造影（CAG）检查,采用Gensini评分。酶联免疫法测定MCP-1浓度,PCR-RFLP方法检测MCP-1-2518G／A位点多态性,研究MCP-1-2518G／A基因多态性与冠心病的相关性。结果（1）MCP-1-2518G／A基因多态性ACS组GG型基因和G等位基因频率分布较SAP组及正常对照组升高[GG型基因：ACS组（33．4％）,SAP组（24．2％）,对照组（15．0％）。P〈0．05;G等位基因频率：ACS组（51．1％）,SAP组（40．4％）,对照组（31．7％）,P〈0．05],ACS组AA型基因及A等位基因较SAP组及正常对照组降低[AA型基因：ACS组（31．1％）,SAP组（43．3％）,对照组（51．7％）,P〈O．05;A等位基因频率：ACS组（48．9％）,SAP组（59．6％）,对照组（68．3％）,P〈0．05]。（2）三种基因型间MCP．1浓度比较,GG型MCP-1浓度较AG型及AA型升高[GG型基因：（153±22）ng／L,AG型基因：（136±18）ng／L,AA型基因：（124±15）ng／L,（P〈0．05）]。（3）多元回归分析冠脉病变Gensini评分与低密度脂蛋白-胆固醇、空腹血糖、MCP-1GG型基因成正相关（P〈0．05）,高密度脂蛋白-胆固醇与冠状动脉狭窄程度呈负相关（P〈0．05）。结论MCP-1-2518G／A基因多态性与冠心病严重程度相关;MCP-1-2518G／A基因多态G等位基因能通过增强MCP-1表达参与冠心病发病。     

PAI-1基因多态性与2型糖尿病的相关性

目的分析2型糖尿病患者（T2DM）纤溶酶原激活物抑制物（PAI）-1基因型及分布频率,探讨PAI-1基因多态性与T2DM的关系。方法观察组为34例T2DM患者,对照组为39例健康体检正常者,采用等位基因特异性引物PCR扩增技术检测各组人群PAI-1基因多态性,两组人群血浆PAI-1含量检测采用美国USCNLIFE原装人PAI-1 ELISA试剂盒,酶标仪450nm波长下测定吸光度（OD值）,两次平行测定取均值计算样品PAI．1水平。结果观察组与对照组相比PAI-1基因型频率及等位基因频率均有显著性差异（r=24．127,P〈0．001;X^2=7．312,P〈0．05）。观察组4G等位基因频率明显高于对照组,有显著性差异（X^2=6．280,P〈0．05）。观察组血浆PAI-1水平明显高于对照组（t=10．7,P〈0．01）,观察组内比较4G／4G者血浆PAI-1含量明显高于4G／5G和5G／5G者,有显著性差异（F=21．02,P〈0．001）。结论PAI-1基因多态性与T2DM间存在一定的关联性,其中4C等位基因可能是T2DM发病的危险因子。     

甘肃地区PRKAA2基因单核苷酸多态性与2型糖尿病及脂联素、抵抗素关系的研究

目的 探讨甘肃地区PRKAA2基因rs2746342（G／T）单核苷酸多态性与T2DM及血清脂联素（APN）、抵抗素（Resistin）的关系。方法甘肃地区T2DM患者163例和正常对照组86名,两组年龄、性别匹配,采用聚合酶链反应／DNA限制性片段长度多态性（PCR／RFLP）、酶联免疫分析（ELISA）检测其基因多态性、空腹C肽（FC-P）、APN、Resistin,同时测身高、体重、血压、BMI、空腹血糖、血脂等。结果（1）T2DM组与正常对照组的基因型和等位基因频度分布存在显著差异（P〈0．05）;（2）T2DM组各基因型T／T、G／T、G／G中Resistin、TG、TC、LDL-C、FC-P依次降低,APN、HDL-C依次增高（P〈0．05）;（3）APN水平在糖尿病超重组低于糖尿病正常体重组和对照组,Resistin水平在糖尿病超重组高于糖尿病正常体重组和对照组（P〈0．05）;（4）相关分析表明APN水平与BMI、血压负相关,与C-肽正相关（P〈0．05）,Resistin水平与BMI、血压正相关,与G肽负相关（P〈0．05）;（5）T2DM超重组较T2DM正常体重组和正常对照组TG、LDL-C水平升高（P〈0．05）,HDL-C水平降低（P〈0．05）。结论甘肃地区PRKAA2基因rs2746342（G／T）单核苷酸基因多态性可能与T2DM及胰岛素抵抗、血清APN、Re—sistin水平关联。     

内皮素转化酶1启动子区T-839G基因多态性与颈动脉粥样硬化的相关性

目的研究内皮素转化酶1（ECE-1）启动子T-839G基因多态性与颈动脉粥样硬化的相关性。方法选择经DSA或CTA、MRA诊断的颈动脉粥样硬化患者及与之年龄和性别相匹配的对照者,各518例。采用多聚酶链反应-限制性片段长度多态性（PCR—RFLP）的方法检验ECE-1启动子区T-839G基因多态性。结果两组TT、TG、GG基因型分布差异无统计学意义（χ^2=4．674,P〉0．05）,颈动脉粥样硬化组等位基因频率T略高于对照组（92．3％,89．8％）,G略低于对照组（7．7％,10．2％）,差异有统计学意义（χ^2=3．993,P〈0．05）。两组总计（GG＋TG）／TT的基因型频率差异虽无统计学意义,但按性别和年龄分层后,显示女性和〈64岁者（GG＋TG）／TT基因型频率对照组均高于颈动脉粥样硬化组（女性：OR=0．59;95％CI：0．37～0．94;P=0．03。〈64岁者：OR=0．61;95％CI：0．38～0．97;P=0．04）结论ECE-1启动子区T-839G多态位点G等位基因可能降低女性及年龄〈64岁者颈动脉粥样硬化发生的危险性。     

壮族人群MCP-1基因多态性与2型糖尿病及糖尿病肾病相关性研究

目的探讨壮族人群单核细胞趋化蛋白1（MCP-1）启动子区A-2518G基因多态性与血清中MCP-1含量与糖尿病（DM）及糖尿病肾病（DN）的关系。方法采用聚合酶链反应-限制性片段长度多态性方法,对150例T2DM患者[正常白蛋白尿（D0）组51例,微量白蛋白尿（D1）组54例,临床白蛋白尿（Dz）组45例]和70名健康对照者（NC组）的MCP-1基因启动子区A-2518G多态性进行检测,比较各组间基因型频率和等位基因频率。同时检测66例T2DM、70名NC者MCP-1水平。结果DN（D1＋D2）组的GA、AA基因型频率和A等位基因频率高于D0组（P〈0．01）。D1和D2组间基因型频率和等位基因频率无统计学差异。D0组与NC组间基因型频率有统计学差异,但等位基因频率无统计学差异。GG、GA的人群MCP-1表达水平较AA型者高（P〈0．05）。Logistic回归分析表明MCP-1基因启动子区A-2518G多态性、病程与DN显著相关,GA和AA基因型及病程〉5年是DN发生的危险因素。结论壮族人群中MCP-1基因启动子区A-2518GGA、AA基因型可能是DN发生的危险因素;病程〉5年可能是DN进展的危险因素。MCP-1启动子区A-2518G基因多态性可影响MCP-1水平。     

细胞色素P450表氧化酶2J2基因G312R多态性与脑卒中的关系

目的探讨我国汉族人群细胞色素P450表氧化酶2J2(CYP2J2)基因G312R多态性与脑卒中的关系。方法选择脑卒中病例180例和性别、年龄相匹配的健康人群190例,采用PCR-RFLP方法进行CYP2J2基因G312R多态性分析。结果370例均为野生型,未发现杂合子和突变后纯合子。结论CYP2J2基因G312R突变不是我国部分人群缺血性脑卒中、脑出血发病的遗传危险因素。     

Promoter polymorphism G-50T of a human CYP2J2 epoxygenase gene is associated with common susceptibility to asthma

BACKGROUND: Cytochrome P-450 2J2 (CYP2J2) has recently been shown to be an important enzyme in the metabolism of epoxygenase-derived eicosanoids that play important functional roles in pulmonary physiology and may contribute to the pathogenesis of asthma. STUDY OBJECTIVE: The focus of our pilot study was to evaluate whether common polymorphism G-50T within the proximal promoter of human CYP2J2 gene is associated with the susceptibility to bronchial asthma. Design and participants: A total of 429 unrelated Russian subjects were recruited in this case-control study, including 215 sex-matched and age-matched patients with asthma and 214 healthy control subjects. The blood samples were analyzed for genetic polymorphism G-50T in the CYP2J2 gene by polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: The frequency of variant allele -50T of the CYP2J2 gene was significantly higher in asthmatic patients than in healthy subjects (odds ratio [OR], 5.04; 95% confidence interval [CI], 1.99 to 12.77; p = 0.0003). In addition, the heterozygous genotype -50GT of the CYP2J2 gene was found to be significantly associated with susceptibility to allergic asthma (OR, 5.40; 95% CI, 2.05 to 14.26; p = 0.0003) as well as nonallergic asthma (OR, 5.77; 95% CI, 1.84 to 18.10; p = 0.004). The associations of the CYP2J2 gene G-50T polymorphism with asthma remained significant after adjustment for age and gender using multiple logistic regression analysis. CONCLUSIONS: Our data demonstrate for the first time that the CYP2J2 gene might be considered as a novel candidate gene for common susceptibility to asthma and highlight the importance of the P-450 epoxygenase pathway of metabolism of arachidonic acid in the pathogenesis of the disease.     

EPHX1 rs2234922 polymorphism and lung cancer susceptibility in Asian populations: a meta-analysis

Objective

Polymorphisms of epoxide hydrolase 1 (EPHX1) rs2234922 have been reported to be associated with variations in EPHX1 activity. Many studies have investigated the association between EPHX1 rs2234922 polymorphism and lung cancer risk, but their results have been inconsistent. The purpose of this study was to perform a meta-analysis of all eligible studies to derive a more precise estimation of the associations of EPHX1 rs2234922 polymorphism with lung cancer.

Methods

The PubMed was searched for case-control studies published up to Oct 01, 2014. Data were extracted and pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated. The pooled ORs for the risk associated with the genotypes of homozygote G/G and G allele carriers (A/G + G/G) with the A/A genotype were calculated. Heterogeneity assumption was checked by the chi-square-based Q-test. A P value greater than 0.10 for the Q-test indicates a lack of heterogeneity among studies, so the pooled OR estimate of the each study was calculated by the fixed-effects model (the Mantel-Haenszel method). Otherwise, the random-effects model (the DerSimonian and Laird method) was used.

Results

In this meta-analysis, we assessed eight published studies involving comprising 1,175 cases and 1,550 controls of the association between EPHX1 rs2234922 polymorphism and lung cancer risk. For the homozygote G/G and G allele carriers (A/G + G/G), the pooled ORs were 1.47 (95% CI: 1.18-1.79, P=0.007 for heterogeneity) and 1.36 (95% CI: 1.14-1.62, P=0.828 for heterogeneity), when compared with the homozygous wild-type genotype (A/A).

Conclusions

EPHX1 rs2234922 polymorphism contributes to risk of lung cancer among Asian population.     

环氧化物水解酶基因多态性与新疆哈萨克族、汉族原发性高血压的相关性研究

目的 探讨环氧化物水解酶( EPHX2)基因rs751141位点基因多态性与新疆哈萨克族、汉族原发性高血压之间的相关性.方法 分别选择新疆哈萨克族267例,汉族原发性高血压患者368例,同时选取哈萨克族、汉族正常对照组284例和348例,用Hardy-Weinberg平衡检验样本群体代表性,采用TaqMan探针法对EPHX2基因rs751141位点基因多态性进行检测.结果 新疆汉族原发性高血压组rs751141G/A多态位点GA+ AA基因型的分布频率(40.2％)明显低于正常对照组(52.0％),差异具有统计学意义(P＜0.01),而新疆哈萨克族原发性高血压组与正常对照组中rs751141G/A基因多态性比较差异均无统计学意义(P＞0.05).结论 EPHX2基因rs751141 G/A等位基因多态性与新疆哈萨克族原发性高血压无显著相关性,EPHX2基因rs751141G/A等位基因多态性与新疆汉族原发性高血压均显著相关,EPHX2基因rs751141位点的A等位基因可能是新疆汉族原发性高血压病的独立的保护因子.     

细胞色素P45O 2E1基因多态性与抗结核药物致肝损伤的关系

目的 探讨细胞色素P450(CYP)2E1基因多态性与抗结核药物所致肝损伤(ADIH)的关系.方法 采用病例对照研究设计,选择符合条件的339例结核患者为研究对象,调查其一般情况及肝功能,聚合酶链反应-限制性片段长度多态性分析进行基因分型.数据行单因素和多因素Logistic回归分析.结果 ADIH病例组103例结核患者CYP 2E1的7632T/A、101 9C/T、1259G/C等位基因频率分别为17.5%、26.2%和27.2%,对照组236例结核患者分别为29.7%、39.4%和40.7%(x2=5.539,P＜0.05;x2=5.458,P＜0.05;x2=5.628,P＜0.05).经多因素Logistic回归分析调整了性别、职业、饮酒等危险因素后,7632T/A、1019C/T、1259G/C位点多态性与ADIH的发生仍有相关性,且7632T/A与1019C/T及1259G/C位点野生基因型在ADIH发生过程中起协同作用.结论 携带CYP 2 E1的7632T/A、1019C/T和1259G/C位点野生基因型的个体发生ADIH的危险性增高,且在ADIH的发病过程中起协同作用.     

CYP1A1, CYP2E1 and EPHX1 polymorphisms in sporadic colorectal neoplasms

AIM To investigate the contribution of polymorphisms in the CYP1A1, CYP2E1 and EPHX1 genes on sporadic colorectal cancer(SCRC) risk. METHODS Six hundred forty-one individuals(227 patients with SCRC and 400 controls) were enrolled in the study. The variables analyzed were age, gender, tobacco and alcohol consumption, and clinical and histopathological tumor parameters. The CYP1A1 *2A, CYP1A1 *2C CYP2E1 *5B and CYP2E1 *6 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The EPHX1 Tyr113 His, EPHX1 His139 Arg and CYP1A1 *2C polymorphisms were detected by real-time PCR. Chisquared test and binary logistic regression were used in the statistical analysis. Haplotype analysis was conducted using the Haploview program, version 2.05.RESULTS Age over 6 2 years was a risk factor for SCRC development(OR = 7.54, 95%CI: 4.94-11.50, P 0.01). Male individuals were less susceptible to SCRC(OR = 0.55, 95%CI: 0.35-0.85, P 0.01). The CYP2E1*5B polymorphism was associated with SCRC in the codominant(heterozygous genotype: OR = 2.66, 95%CI: 1.64-4.32, P 0.01), dominant(OR = 2.82, 95%CI: 1.74-4.55, P 0.01), overdominant(OR = 2.58, 95%CI: 1.59-4.19, P 0.01), and log-additive models(OR = 2.84, 95%CI: 1.78-4.52, P 0.01). The CYP2E1*6 polymorphism was associated with an increased SCRC risk in codominant(heterozygous genotype: OR = 2.81, 95%CI: 1.84-4.28, P 0.01; homozygous polymorphic : OR = 7. 3 2, 9 5 % C I : 1.85-28.96, P 0.01), dominant(OR = 2.97, 95%CI: 1.97-4.50, P 0.01), recessive(OR = 5.26, 95%CI: 1.35-20.50, P = 0.016), overdominant(OR = 2.64, 95%CI: 1.74-4.01, P 0.01), and log-additive models(OR = 2.78, 95%CI: 1.91-4.06, P 0.01). The haplotype formed by the minor alleles of the CYP2E1*5B(C) and CYP2E1*6(A) polymorphisms was associated with SCRC(P = 0.002). However, the CYP1A1 *2A, CYP1A1 *2C, EPHX1 Tyr113 His and EPHX1 His139 Arg polymorphisms were not associated with SCRC.CONCLUSION In conclusion, the results demonstrated that CYP2E1*5B and CYP2E1*6 minor alleles play a role in the development of SCRC.     

Association Between NAT2 Polymorphisms and Lung Cancer Susceptibility

To further investigate the association between NAT2 polymorphisms and lung cancer susceptibility.In terms of phenotypes, we investigated the acetylator status of NAT2 polymorphisms associated with lung cancer risk. Additionally, in view of genotypes, we mainly analyzed 5 single nucleotide polymorphisms (SNPs) in NAT2 gene, namely C282T, A803G, C481T, G590A, and G857A. Twenty-six eligible studies were included in our meta-analysis by searching PubMed, Embase, and CNKI databases. We used odds ratios (ORs) with corresponding 95% confidence intervals (CIs) to evaluate the susceptibility to lung cancer associated with NAT2 polymorphisms.Overall, based on phenotypes, the pooled ORs showed no significant association between NAT2 polymorphisms and lung cancer susceptibility. In the subgroup analyses by ethnicity and source of control, there was still no significant association. In terms of genotypes, overall, no obvious relationship was observed between NAT2 polymorphisms and lung cancer risk. But increased risk of lung cancer was found in association with NAT2 C282T polymorphism (TT vs. CC + TC: OR = 1.58, 95% CI = 1.11–2.25).Our meta-analysis demonstrates that TT genotype in NAT2 C282T polymorphism may be a risk factor for lung cancer susceptibility. Additionally, the acetylator status of 5 SNPs in NAT2 gene may not be associated with lung cancer risk.     

EPHX1 Gene Polymorphisms in Alcohol Dependence and their Distribution among the Indian Populations

Background: The microsomal epoxide hydrolase is a phase II enzyme of the biotransformation. The human epoxide hydrolase 1 (EPHX1) gene lies in the chromosomal region 1q42.1 and exhibits polymorphism. Two single nucleotide polymorphisms (SNPs) have been described in the coding region of the EPHX1 gene that produces two protein variants. Subjects and methods: A total of 604 samples belonging to 13 Indian populations were included in this study. Based on the DSM-IV criteria, 184 individuals from Kota population were classified into alcoholism cases (100) and controls (84). Genotypes of Tyr113His and His139Arg polymorphisms in the EPHX1 gene were determined using PCR and sequencing. Associations were tested using Pearson’s χ² test and haplotype analyses. Results: We found significant association between EPHX1 gene Tyr113His polymorphism and alcoholism in the Kota population (T vs. C: OR = .615, 95% CI = .399–.949, p = .027; TT vs. CC + CT: OR = .536, 95% CI = .297–.969, p = .038). The very slow activity haplotype CA (113His–139His) was also found to be associated with alcohol dependence (p = .048). Analysis of additional populations demonstrated that the Tyr113His polymorphism significantly deviated from Hardy–Weinberg equilibrium in four populations but only one population deviated for the His139Arg locus. All populations shared the four possible two-site haplotypes. Linkage disequilibrium between these two loci was not significant in any of the population studied. Conclusion: EPHX1 gene polymorphisms and haplotypes are associated with an increased risk for alcoholism in the Kota population. This is the first report from India that will serve as a template for future investigations of the prevalence of EPHX1 alleles in association with various clinical entities.     

"CYP2D6"基因多态性和NSCLC靶向治疗后肝损伤、皮疹及腹泻的相关性

目的比较非小细胞肺癌(non-small cell lung cancer, NSCLC)患者CYP2D6×10与CYP2D6×5基因多态性的差异与经靶向治疗(吉非替尼、厄洛替尼、克唑替尼)后出现肝损伤，皮疹，腹泻不良反应的相关性，探索靶向药物治疗常见不良反应与CYP2D6基因多态性的关联。 方法选择新疆医科大学附属肿瘤医院2016年1月至2019年12月经靶向治疗(吉非替尼、厄洛替尼、克唑替尼)的NSCLC患者，采用限制性片段长度多态性聚合酶链反应(polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP)检测患者CYP2D6×10与CYP2D6×5基因型分布及等位基因频率。比较基因型分布差异和等位基因差异在出现肝损伤、腹泻、皮疹组与无患者组的差异。 结果CYP2D6×10基因多态性及等位基因频率在发生肝损害组与无肝损害组差异有统计学意义(P<0.05)，皮疹组和腹泻组均与CYP2D6×10基因多态性及等位基因频率差异无相关性。腹泻有关的唯一相关因素是否有化疗史(P＝0.002)，皮疹相关的因素是分期P＝0.000。 结论NSCLC靶向治疗药物性肝损伤的预测方面CYP2D6基因多态性可能是其中有效的指标之一，可指导NSCLC患者临床用药。