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。     

GSTM1和CYP2E1基因多态性与非小细胞肺癌遗传易感性的相关性研究

目的探讨细胞色素p4502E1基因(CYP2EI)和谷胱甘肽转硫酶MI(GSTM1)基因多态性与深圳地区非小细胞肺癌遗传易感性的相关性。方法收集2014年2月~2016年10月在深圳各医院就诊并确诊为非小细胞肺癌患者和同期住院的肺良性疾病患者各71例,采用PCR-RFLP和PCR法分别检测CYP2E1基因的RsaⅠ/PstⅠ和GSTM1基因多态性,并分析基因多态性与非小细胞肺癌遗传易感性之间的相关性。结果非小细胞肺癌组和肺良性疾病组患者CYP2E1基因Rsa I/Pst I多态性的三种基因型检出频率差异无统计学意义(χ~2=0.891~1.205,P0.05);非小细胞肺癌组GSTM1(–)基因型频率为61.79%,显著高于肺良性疾病组的36.62%,两者频率的差异有统计学意义(χ~2=5.019,P0.05);携带GSTM1(–)基因型的个体患非小细胞肺癌的危险性显著高于GSTM1(+)基因型的个体(OR=2.095,95%CI=1.104~3.173,P=0.032);与携带cl/c2或c2/c2基因型的不吸烟个体比较,携带cl/cl基因型的吸烟者患非小细胞肺癌的风险显著增加(OR=3.415,95%CI=1.092~11.214,P=0.028);携带cl/cl和GSTM1(–)基因型的个体患非小细胞肺癌的风险显著高于携带GSTM1(+)和cl/c2或c2/c2基因型的个体(OR=3.518,95%CI=1.106~l2.812,P=0.045)。在不吸烟人群中,携带GSTM1(–)和cl/cl基因型的人群患非小细胞肺癌的风险显著高于携带GSTM1(+)和cl/c2或c2/c2基因型的人群(OR=2.917,95%CI=1.004~8.316,P=0.043),且携带有GSTM1(–)和cl/c2或c2/c2基因型的人群患非小细胞肺癌的风险同样高于携带GSTM1(+)和cl/c2或c2/c2基因型的人群(OR=14.062,95%CI=1.362~147.256,P=0.029)。结论 GSTM1(–)基因型是深圳地区人群患非小细胞性肺癌的风险因素之一;同时携带CYP2E1的cl/cl和GSTM1(–)基因型可增加吸烟和不吸烟人群患非小细胞肺癌的风险。     

鼻咽癌患者谷胱甘肽S转移酶M1基因多态性研究

目的探讨鼻咽癌(NPC)患者的GSTM1基因多态性.方法采用内参照PCR对NPC患者的基因组DNA进行GSTM1基因型检测.结果NPC患者GSTM1空白基因型频率为60.0%,对照组为45.0%,两者差异有显著性(P<0.05),其OR=1.833,95%CI=1.046～3.147;鳞癌的空白基因型频率为60.5%,明显高于腺癌的50.0%(χ2=5.406,P<0.01);吸烟者空白基因型个体患鼻咽癌的危险性显著增加(OR=2.813,95%CI=1.353～6.012,P<0.01),而不吸烟者的危险性增加不明显(P>0.05).结论GSTM1基因多态性与NPC患者的遗传易感有关,与NPC的病理类型也有关,吸烟者的GSTM1空白基因型个体更易患NPC.     

鼻咽癌患者谷胱甘肽S转移酶M_1基因多态性研究

目的探讨鼻咽癌 (NPC)患者的GSTM1基因多态性。方法采用内参照PCR对NPC患者的基因组DNA进行GSTM1基因型检测。结果NPC患者GSTM1空白基因型频率为 6 0 .0 % ,对照组为 4 5 .0 % ,两者差异有显著性 (P <0 .0 5 ) ,其OR =1.833,95 %CI =1.0 4 6～ 3.14 7;鳞癌的空白基因型频率为 6 0 .5 % ,明显高于腺癌的5 0 .0 % (χ2 =5 .4 0 6 ,P <0 .0 1) ;吸烟者空白基因型个体患鼻咽癌的危险性显著增加 (OR =2 .813,95 %CI=1.35 3～ 6 .0 12 ,P <0 .0 1) ,而不吸烟者的危险性增加不明显 (P >0 .0 5 )。结论GSTM1基因多态性与NPC患者的遗传易感有关 ,与NPC的病理类型也有关 ,吸烟者的GSTM1空白基因型个体更易患NPC     

细胞色素P450 2E1基因多态性与胃癌易感性的关系

目的:探讨细胞色素P4502E1(CYP2E1)基因多态性与胃腺癌易感性的关系,为胃癌高危人群的筛选和预防控制工作提供科学依据。方法:选择41例胃腺癌患者(胃癌组)及41例健康对照者(对照组),分别采用PCR-RFLP技术与多重PCR方法,检测CYP2E1基因型,观察其多态性,然后进行统计学分析。结果:CYP2E1C1/C1基因型(纯合子野生型)在胃癌组和对照组中的分布频率分别是61.0%和41.5%,差异具有显著性(χ2=6.71,P<0.05)。结论:CYP2E1C1/C1基因型与胃癌遗传易感性相关。     

慈溪市常见恶性肿瘤与代谢酶基因多态性关系的研究

目的 探讨慈溪市居民常见恶性肿瘤与代谢酶基因多态性关系.方法 分层随机抽取108对研究对象,总计216例血样,剔除不合格研究对象,最后有100对配对个体共200例研究对象完成基因型的检测.采用DNA抽提采用改良盐析法和基因多态性检测.结果 非GSTM1缺陷型有231 bp的片段,非GSTF1缺陷型有120 bp的片段,而所有的样品都有268 bp的-球蛋白的DNA片段.CYP2E1基因第1019CT点突变使RsaI识别位点消失,CYP2E1基因第1259GC点突变产生RsaI识别位点.CYP2EIRsaI CC,CT,TT基因型分布在对照人群中的频率分别为64.0%,35.0%和1.0%,CYP2E1PstI GG,GC,CC基因型分布在对照人群中的频率分别为70.0%,30.0%,0.0%.GSTT1缺陷型与常见恶性肿瘤患病风险没有观察到有统计学意义的相关性效应,OR值分别为1.22(95%CI:0.70～2.13)和0.65(95%CI:0.36～1.20);以CYP2E1PstI野生型(GG基因型)作为参照,CYP2E1RsaI杂和型(GC基因型)患肿瘤的风险增高,其OR值为1.11(95%CI:0.61～2.03).结论 慈溪市正常人群中四个基因位点GSTM1,GSTF1,CYP2E1RsaI,CYP2E1PstI的多态基因型分布与国内报道基本一致,四个位点基因多态性与慈溪市常见恶性肿瘤易感性无统计学意义的关联.     

GSTP1、CYP2E1基因遗传多态性与急性白血病易感性的关系

本研究旨在探讨谷胱甘肽巯基转移酶P1(GSTP1)和细胞色素P4502E1(CYP2E1)基因多态性与急性白血病易感性的关系。采用1∶1配对病例-对照、LDR分型方法对150例急性白血病(AL)患者和150例对照组进行GSTP1和CYP2E1的基因多态性进行检测。结果表明:AL病例组GSTP1基因G等位基因频率(26.7%)和Ile/Val和Val/Val基因型频率(44%)均高于对照组(10%和16%)。携带突变基因型(Ile/Val和Val/Val)个体发生AL的相对风险度为Ile/Ile个体的3.226倍(95%CI=1.527-5.236)。进一步分层分析表明,急性髓系白血病(AML)病例组Ile/Val和Val/Val基因型频率(55.0%)高于对照组(16%)(p<0.05)。携带Ile/Val和Val/Val基因型的个体发生AML的相对风险度为野生基因型(Ile/Ile)个体的2.214倍(95%CI=1.009-3.260)。AL病例组CYP2E1基因C2等位基因频率(16.7%)和C1C2/C2C2基因型频率(30%)均高于对照组(13.9%和26%),但其差异均无统计学意义。进一步分层分析...     

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.     

新生儿CYP1A1、GSTM1、GSTT1基因的多态性分布

目的 研究新生儿CYP1A1、GSTM1、GSTT1基因的多态性分布，为新生儿建立相应基因型记录，达到防病治病的目的。方法 收集新生儿脐血，抽提其中有核细胞的DNA，PCR扩增CYP1A1、GSTM1、GSTT1基因的特征性外显子片段。限制酶切CYP1A1扩增产物，RFLP分析每个标本的基因型；非变性聚丙稀酰胺凝胶电泳分析GSTM1、GSTT1的基因型。结果 CYP1A1、GSYM1和GSTT1基因型均成多态性分布，CYP1A1的基因型分布有3种，分别为A/A基因型占60．9％、A/G基因型占34．5％、G／G基因型占4．5％；GSTM1的基因型有2种分别为GSTM1＋／＋和GSTM1＋／0占85．5％、GSTM1-／-占14．5％。GSTT1基因型分布为GSTT1＋／＋和GSTT1＋／0占76．1％，GSTT10／0为23．6％。结论 在正常出生的新生儿中，他（她）们的代谢酶CYP1A1、GSTM1、GSTT1基因存在着多态性分布的现象。     

吸烟和CYP1A1、GSTM1基因多态对肺癌易感性影响

目的:探讨细胞色素P4501A1(cytochrome P-450 1A1,CYP1A1)与谷胱甘肤硫转移酶M1(glutathione S-transferase M1,GSTM1)基因多态与支气管肺癌的关系.方法:采用PCR限制性片段多态检测法,检测肺癌组103例和正常对照组138例患者的CYP1A1与GSTM1基因多态,以非条件性Logistic回归模型分别对年龄、性别进行校正后计算优势比及95%CI.结果:CYP1A1 ml突变型等位基因频率在对照组和肺癌组分别为27.6%和42.7%;GSTM1的缺陷型基因(D)频率在对照组、肺癌组分别为44.2%和61.2%.Logistic回归分析表明,CYP1A1(w1/m1)杂合型(B型)患肺癌的升高3.19倍,纯合突变型(C型)基因患肺癌的升高2.61倍,GSTM1缺陷型(D)患肺癌危险度升高2.09倍,差异均有统计学意义(P<0.05).GSTMl(D)/CYP1A1(B或C)基因型的个体患肺癌危险度为5.72倍.GSTMI(D)和CYP1A1 ml突变型等位基因均可明显增加鳞癌和小细胞癌的患病危险度.结论:CYP1A ml突变型等位基因和GSTM1(D)均是患肺癌的危险因素.CYP1A m1突变型等位基因和GSTM1(D)存在明显的交互作用,二者与吸烟有协同作用.     

Influence of glutathione S-transferase M1 and T1 genotypes on larynx cancer risk among Korean smokers.

Glutathione S-transferase (GST) isoenzymes are involved in the detoxification of major carcinogens present in tobacco smoke. It is thus conceivable that deficiency in GST activity due to homozygous deletions of the GSTM1 and GSTT1 genes (the null genotypes) may modulate susceptibility to smoking-induced cancers. The influence of the GSTM1 and GSTT1 null genotypes on larynx cancer risk among the Korean population were evaluated using peripheral blood DNA from 82 larynx cancer patients and 63 healthy controls, all of whom were male current smokers. Increased larynx cancer risk was related to the GSTM1 null genotype (odds ratio (OR)=3.53, 95% confidence interval (CI)=1.27-9.83). The OR associated with the GSTT1 null genotype was also increased, but did not reach statistical significance (OR=1.83, 95% CI=0.70-4.79). Individuals lacking both the GSTM1 and GSTT1 genes were at a significantly higher risk for larynx cancer than individuals with both genes present (OR=4.04, 95% CI=1.33-12.30). These data confirm that the GSTM1 null genotype is an important risk modifier for larynx cancer among Korean smokers and combined GSTM1 and GSTT1 null genotypes could be a useful predictor of genetic susceptibility to larynx cancer.     

Relevance of glutathione S-transferase M1 and cytochrome P450 1A1 genetic polymorphisms to the development of head and neck cancers.

BACKGROUND: Cytochrome P450 (CYP) and glutathione S-transferase (GST) gene variants have been intensively investigated for their implication in the development of different neoplasms. METHODS: In the present study, we analyzed genetic polymorphisms of CYP1A1, GSTM1, GSTP1, and GSTT1 in 127 head and neck cancer patients and 151 hospital controls. RESULTS: No significant increase in risk in patients with the GSTM1 null genotype (OR=1.52, 95% CI: 0.93-2.49) or CYP1A1 462Val alleles (OR=1.60, 95% CI: 0.73-3.52) or GSTP1 105Val alleles (OR=0.97, 95% CI: 0.59-1.58) was observed. The GSTT1 null genotype was found in 30.5% of the controls and 21.3% of the head and neck cancer patients (p=0.15). The estimated head and neck cancer risk for the combination of either CYP1A1 Ile462Val or CYP1A1 Val462Val genotype with either GSTP1 Ile105Val or Val105Val genotype (OR=2.89, 95% CI: 0.71-11.71) and for the combination of either CYP1A1 Ile462Val or CYP1A1 Val462Val genotype with GSTT1 null genotype (OR=2.62, 95% CI: 0.64-10.85) suggested the absence of the modifying effect of combined variant alleles on head and neck cancer susceptibility. The joint effect of either CYP1A1 Ile462Val or CYP1A1 Val462Val genotype with GSTM1 null genotype significantly increased the risk of head and neck cancer (OR=7.15, 95% CI: 1.49-34.32). CONCLUSIONS: Our findings corroborate metabolic genes interactions, especially for CYP1A1 462Val alleles and GSTM1 homozygous deletion, in the development of head and neck cancer in the investigated population groups in Poland.     

CYP2E1, GSTM1 and GSTT1 genetic polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity: a nested case-control study

What is Known and Objective: The pathogenic mechanism of antituberculosis drug‐induced hepatotoxicity (ATDH) is thought to involve drug‐metabolizing enzymes including N‐acetyl transferase2 (NAT2), cytochrome P4502E1 (CYP2E1) and glutathione S‐transferase (GST) M1, T1. The associations between genetic polymorphisms of those genes and ATDH have been reported but with inconsistent results. Moreover, most studies were hospital‐based retrospective studies and not prospective. We aimed to investigate possible associations of CYP2E1, GSTM1 and GSTT1 genetic polymorphisms with ATDH using a more robust case–control study nested in a population‐based prospective antituberculosis treatment cohort. Methods: A total of 4304 patients with smear‐positive tuberculosis (TB) who received standard short‐course chemotherapy were monitored for 6–9 months. Incidence density sampling method was adopted to select controls and 4 : 1 matched with each ATDH cases by age (±5 years), sex, treatment history, disease severity and drug dosage. The CYP2E1, GSTM1 and GSTT1 polymorphisms were genotyped using PCR–RFLP and multiplex PCR methods. Conditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI), as well as corresponding P‐values. Results and Discussion: A total of 89 ATDH cases and 356 controls were included in this study. There was no statistically significant association between CYP2E1 RsaI c1/c1 genotype or DraI C/C genotype and ATDH (OR = 0·99, 95% CI:0·62–1·59; OR = 1·13, 95% CI: 0·40–3·20, respectively) compared with CYP2E1 RsaI c1/c2 or c2/c2 genotypes or DraI D/D genotype, or between GSTM1/GSTT1 null genotypes and ATDH (OR = 1·22, 95% CI: 0·76–1·96; OR = 0·96, 95% CI: 0·60–1·52, respectively) compared with non‐null genotypes. What is new and Conclusion: This is the first study of the involvement of CYP2E1, GSTM1 and GSTT1 genetic polymorphisms in ATDH using a nested case–control population‐based prospective cohort design. We could not confirm positive associations of genetic polymorphisms of CYP2E1 RsaI, CYP2E1 DraI, GSTM1 null and GSTT1 null with ATDH reported by various groups, in our Chinese TB population.     

骨髓增生异常综合征患者GSTT1、GSTM1基因分布频率和NQO1基因多态性分析

目的探讨谷胱甘肽S转移酶（GST）基因T1、M1（GSTY1、GSTM1）和苯醌氧化还原酶基因（NQO1C609T）多态性与骨髓增生异常综合征（MDS）易感性及MDS染色体核型异常的关系。方法用多重PCR方法检测52例MDS患者和241名与患者无血缘关系的正常人GSTF1和GSTM1基因型，用PCR-限制性片段长度多态性（RFLP）方法分析NQO1C609T基因型。结果与正常人对照组相比，MDS患者GSTT1和GSTM1无效型（nu11）比例明显增高（P值均〈0．01），其比值比（OR）分别为2．873（95％可信区间：1．491～5．537）和3．591（95％可信区间：1．717～7．508）。染色体核型正常的MDS患者GSTT1无效型比例较正常人对照组显著增高（OR=5．336，P〈0．01），而GSTM1无效型比例与正常人对照组比较差异无统计学意义染色体核型异常的MDS患者GSTM1无效型比例较正常人对照组显著增高（OR=3．740，P〈0．01），而GSTT1无效型比例与正常人对照组比较差异无统计学意义MDS患者的NQI1C609T各基因型与正常人对照组差异无统计学意义。结论GSTT1和GSTM1基因无效型可能与MDS发生相关，对判断MDS患者是否出现染色体核型异常有一定意义。     

Cytochrome P450 2D6 and glutathione S-transferase M1 genotypes and migraine

BACKGROUND: Migraine is thought to be a disease of the brain and trigeminovascular system. Migraine patients often claim that stress, food, and beverages trigger their attacks. Chemical substances in these foodstuffs with the property of triggering migraine attacks have not yet been characterised. Cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase M1 (GSTM1) are thought to be present in the brain. They metabolise numerous environmental compounds. The genes exhibit genetic polymorphism that is associated with altered enzyme activity. The aim of this study was to determine if the genotypes of these two enzymes are associated with migraine. MATERIALS AND METHODS: The study included 100 female patients and 245 female controls from the general population. Genomic DNA was isolated from whole blood. Allele specific PCR methods were used to identify the normal CYP2D6*1 allele and the mutated CYP2D6*3 and CYP2D6*4 alleles. Initially all samples were genotyped only for GSTM1 plus (+) and GSTM1 null (-) variants. All samples positive for GSTM1 were further analysed for the presence of allelic variants GSTM1*A and GSTM1*B. RESULTS: None of the CYP2D6 and GSTM1 genotypes was associated with migraine. We observed an odds ratio (OR) for the poor metaboliser genotype of CYP2D6 of 1.4 (95% CI = 0.5-3.6) and for the GSTM1 null genotype of 1.0 (95% CI = 0.6-1.5). CONCLUSION: The results of this study indicate that deficient metabolism because of mutated CYP2D6 alleles or GSTM1 allele variants is not important in the aetiology of migraine.     

Polymorphisms of cytochrome P450 1A1, glutathione S-transferase class mu, and tumour protein p53 genes and the risk of developing gallbladder cancer in Japanese

OBJECTIVES: To examine the relationship between genetic polymorphisms of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase class mu (GSTM1), and tumour protein p53 (TP53) genes, and gallbladder cancer (GBC) risk, a case-control study was conducted. DESIGN AND METHODS: Genotypes of CYP1A1 T3801C, CYP1A1 Ile462Val, GSTM1, and TP53 Arg72Pro were determined in 54 cases of GBC and 178 controls. RESULTS: The age-adjusted odds ratios (ORs) for the Ile/Val genotype of CYP1A1 Ile462Val polymorphism in women and the Arg/Pro genotype of TP53 Arg72Pro polymorphism in men were observed to be 2.70 (95% CI: 1.14-6.40) and 4.32 (95% CI: 1.08-17.2), respectively. No significant differences in the genotypic frequencies of CYP1A1 T3801C and GSTM1 polymorphisms were observed between controls and cases in both men and women. CONCLUSION: These results suggest that the Val allele of CYP1A1 Ile462Val polymorphism and the Pro allele of TP53 Arg72Pro polymorphism contribute to an increased risk of GBC among Japanese women and men, respectively.     

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.

     

Glutathione-S-transferase (GST) M1 null genotype and combined GSTM1 and GSTT1 null genotypes are risk factors for increased serum gamma-glutamyltransferase in valproic acid-treated patients

BACKGROUND: This study was designed to verify whether the glutathione S-transferase (GST) genotypes affect mild hepatotoxicity in valproic acid (VPA)-treated patients. METHODS: The association between the GSTM1 and GSTT1 genotypes, and the levels of aminotransferases and total bilirubin was retrospectively investigated in 149 Japanese epileptic patients treated with VPA. RESULTS: The adjusted odds ratio (OR) of the GSTM1- vs. GSTM1+ genotype and the GSTM1-/GSTT1-vs. GSTM1+/GSTT1+ genotypes for gamma-glutamyltransferase (GGT) increase over the upper limit of normal were 2.8 [95% confidence interval (CI): 1.1-7.2] and 6.5 (95% CI: 1.5-28.0), respectively. The GSTT1 genotypes alone did not significantly affect the liver function tests. The alanine aminotransferase, aspartate aminotransferase and (gamma-glutamyltransferase) GGT levels in patients treated with VPA >6 months were significantly higher in the GSTM1- than GSTM1+ genotype. The GGT levels were significantly higher in the older subjects receiving polytherapy, and the effects of the polytherapy and age were greater in the GSTM1- genotype. CONCLUSIONS: The GSTM1- and GSTM1-/GSTT1- genotypes may be a genetic risk factor for the increase of GGT in VPA-treated patients. However, it was not possible to clarify whether the GGT increase was caused by VPA-induced hepatotoxicity or not.     

Genetic polymorphism of GSTT1 and GSTM1 and susceptibility to chronic obstructive pulmonary disease (COPD)

Background

Chronic obstructive pulmonary disease (COPD) represents a major public health care problem worldwide due to its increasing prevalence, morbidity and mortality. Chronic obstructive pulmonary disease is known to be the fourth leading cause of death and the only cause of death, which is increasing. It is generally accepted that cigarette smoking is the most important risk factor for COPD. Nevertheless, only 10% to 20% of chronic smokers develop the severe impairment of pulmonary functions associated with COPD. This indicates the presence of genetic predisposing factors in its pathogenesis.

Objective

To test the hypothesis that genetic polymorphism of glutathione S-transferase θ 1 (GSTT1)and/or glutathione S-transferase μ 1 (GSTM1) is associated with COPD in smokers.

Materials and Methods

A case-control study was done on 34 patients with COPD and 34 matched controls. DNA was extracted from white blood cells by salting out method. GSTT1 and GSTM1 genotypes were amplified by polymerase chain reaction. The fragments were then analyzed by agarose gel electrophoresis. Statistical analysis was done using SPSS program.

Results

The frequency of carriers of null GSTT1 genotype was 50% among cases compared to 44.1% in the control group. Carriers of null GSTT1 were at minor risk of developing COPD when compared with carriers of the wild GSTT1 genotype (OR, 1.3; 95% CI, 0.5-3.3). In case of GSTM1, the frequency of carriers of null GSTM1 genotype was 52.9% among cases compared to 26.5% in controls. Carriers of null GSTM1 were at much higher risk of developing COPD (OR, 3.13; 95% CI, 1.1-8.6). Furthermore, the risk of developing COPD was increased among carrier of null GSTT1 &; GSTM1 haplotype (OR, 3.6; 95% CI, 1.1-11.6).

Conclusion

Carriers of null GSTM1 genotype were at high risk of developing COPD especially when they were null GSTT1 and GSTM1 haplotype.     

Beta-adducin（Add2）基因rs3755351多态性与高血压遗传易感的相关性研究

目的探讨Beta-adducin（Add2）基因的rs3755351单核苷酸多态性与福建和广东人群中高血压发病的相关性。方法应用MassARRAY-IPLEX技术和基质辅助激光解吸电离飞行时间质谱平台（Matrix-assisted laser desorption/ionization time of fight mass spectrometry,MALDI-TOF-MS）对广东和福建940例高血压患者和944名健康查体者对照进行Add2基因rs3755351位点的基因分型。用χ2检验统计分析病例组和对照组基因型和等位基因的频率;采用非条件Logistic回归分析,计算比值比（OR）和95%CI,评价多态性位点与高血压遗传易感性的相关性。结果 Add2基因rs3755351多态位点有AA,AC和CC三种基因型,在隐性模型中,Add2基因的rs3755351多态位点AA、AC-CC基因型在福建高血压人群中的分布频率为10.5%和89.5%,与对照组（14.2%、85.8%）相比差异有统计学意义（P〈0.05）,与AC或CC基因型相比,携带AA基因型能显著降低患高血压的发病危险（OR=0.65,95%CI：0.43~0.99,P=0.044）;rs3755351的AA、AC和CC基因型在广东高血压人群中的分布频率为15.1%、53.0%和31.8%,与对照组（12.4%、52.4%和35.2%）相比差异无统计学意义（P〉0.05）。结论 Add2基因的rs3755351多态位点与福建人群的高血压遗传易感性相关,与AC或CC基因型相比,携带AA基因型能显著降低患高血压的发病危险;rs3755351在广东人群中未发现与高血压的遗传易感性相关。