Pooled analysis and meta-analysis of the glutathione S-transferase P1 Ile 105Val polymorphism and bladder cancer: a HuGE-GSEC review

The glutathione S-transferase P1 genotype (GSTP1) is involved in the inactivation of cigarette smoke carcinogens, and sequence variation in the gene may alter bladder cancer susceptibility. To examine the association between GSTP1Ile 105Val and bladder cancer, the authors undertook a meta- and pooled analysis. Summary crude and adjusted odds ratios and corresponding 95% confidence intervals were pooled by using a random-effects model. In the meta-analysis (16 studies, 4,273 cases and 5,081 controls), the unadjusted summary odds ratios for GSTP1 Ile/Val and Val/Val compared with GSTP1 Ile/Ile were 1.54 (95% confidence interval: 1.21, 1.99; p < 0.001) and 2.17 (95% confidence interval: 1.27, 3.71; p = 0.005). The association appeared to be the strongest in Asian countries. When the analysis was limited to European descendents (nine studies), the summary odds ratio decreased (odds ratio = 1.24, 95% confidence interval: 1.00, 1.52) (Q = 17.50; p = 0.02). All relevant data previously contributed to the International Study on Genetic Susceptibility to Environmental Carcinogens were pooled (eight studies, 1,305 cases and 1,558 controls). The summary odds ratios were similar to the ones from the meta-analysis. Case-only analyses did not detect an interaction between the GSTP1 genotype and smoking status (never/ever). GSTP1 Ile 105Val appears to be associated with a modest increase in the risk of bladder cancer.     

铀矿工GSTP1基因多态与MGMT基因和p16基因甲基化的关系

目的探讨氡职业暴露人群谷胱甘肽S-转移酶P1(GSTP1)基因多态与痰细胞6-氧-甲基嘌呤-DNA甲基转移酶(MGMT)和p16基因甲基化的关系。方法用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)确定70例氡职业暴露人群GSTP1的基因型;用聚合酶链反应-甲基化特异性法(MSP)确定痰细胞中MGMT和p16基因的甲基化与非甲基化状态。结果在70名铀矿工中,GSTP1基因A105G位点的纯合子(Ile/Ile)42例,杂合子(Ile/Val)25例和纯合子(Val/Val)3例。MGMT、p16基因甲基化率和总甲基化率分别为14.2%、8.6%和18.6%。与携带Ile/Ile人群相比,携带异常等位基因(Ile/Val与Val/Val)的人群MGMT基因甲基化和总甲基化率增加[P=0.037,OR=4.8,95%CI(1.1~21.0);P=0.016,OR=5.1,95%CI(1.4~19.6)];p16基因甲基化率差异无统计学意义[P=0.057,OR=4.6,95%CI(0.8~29.2)]。结论GSTP1(A105G)基因多态性与氡致MGMT基因甲基化和总甲基化的易感性有关。     

The influence of genetic polymorphisms of GSTP1 on the development of asbestosis

OBJECTIVE: Genetic factors play an important role in the development of asbestosis. The aim of this study was to investigate whether genetic polymorphisms of glutathione S-transferase (GST) P1 represent a risk factor for this disease. METHODS: The study population included 262 workers with asbestosis and 265 matched controls. Information on cumulative asbestos exposure was available. A real-time PCR based on the 5' nuclease assay was designed for the analysis of GSTP1 Ile105Val and Ala114Val polymorphisms. RESULTS: Asbestosis was associated with GSTP1 genotype coding for an enzyme with high conjugation capacity versus genotypes resulting in intermediate and low enzyme activity (odds ratio = 1.49, confidence interval = 1.06-2.10). CONCLUSIONS: The key finding of the study was that GSTP1 genotype coding for an enzyme with high conjugation capacity significantly increases the risk of developing asbestosis.     

GSTP1 and TNF Gene Variants and Associations between Air Pollution and Incident Childhood Asthma: The Traffic,Asthma and Genetics (TAG) Study

Background: Genetics may partially explain observed heterogeneity in associations between traffic-related air pollution and incident asthma.Objective: Our aim was to investigate the impact of gene variants associated with oxidative stress and inflammation on associations between air pollution and incident childhood asthma.Methods: Traffic-related air pollution, asthma, wheeze, gene variant, and potential confounder data were pooled across six birth cohorts. Parents reported physician-diagnosed asthma and wheeze from birth to 7–8 years of age (confirmed by pediatric allergist in two cohorts). Individual estimates of annual average air pollution [nitrogen dioxide (NO₂), particulate matter ≤ 2.5 μm (PM_2.5), PM_2.5 absorbance, ozone] were assigned to each child’s birth address using land use regression, atmospheric modeling, and ambient monitoring data. Effect modification by variants in GSTP1 (rs1138272/Ala¹¹⁴Val and rs1695/IIe¹⁰⁵Val) and TNF (rs1800629/G-308A) was investigated.Results: Data on asthma, wheeze, potential confounders, at least one SNP of interest, and NO₂ were available for 5,115 children. GSTP1 rs1138272 and TNF rs1800629 SNPs were associated with asthma and wheeze, respectively. In relation to air pollution exposure, children with one or more GSTP1 rs1138272 minor allele were at increased risk of current asthma [odds ratio (OR) = 2.59; 95% CI: 1.43, 4.68 per 10 μg/m³ NO₂] and ever asthma (OR = 1.64; 95% CI: 1.06, 2.53) compared with homozygous major allele carriers (OR = 0.95; 95% CI: 0.68, 1.32 for current and OR = 1.20; 95% CI: 0.98, 1.48 for ever asthma; Bonferroni-corrected interaction p = 0.04 and 0.01, respectively). Similarly, for GSTP1 rs1695, associations between NO₂ and current and ever asthma had ORs of 1.43 (95% CI: 1.03, 1.98) and 1.36 (95% CI: 1.08, 1.70), respectively, for minor allele carriers compared with ORs of 0.82 (95% CI: 0.52, 1.32) and 1.12 (95% CI: 0.84, 1.49) for homozygous major allele carriers (Bonferroni-corrected interaction p-values 0.48 and 0.09). There were no clear differences by TNF genotype.Conclusions: Children carrying GSTP1 rs1138272 or rs1695 minor alleles may constitute a susceptible population at increased risk of asthma associated with air pollution.Citation: MacIntyre EA, Brauer M, Melén E, Bauer CP, Bauer M, Berdel D, Bergström A, Brunekreef B, Chan-Yeung M, Klümper C, Fuertes E, Gehring U, Gref A, Heinrich J, Herbarth O, Kerkhof M, Koppelman GH, Kozyrskyj AL, Pershagen G, Postma DS, Thiering E, Tiesler CM, Carlsten C, TAG Study Group. 2014. GSTP1 and TNF gene variants and associations between air pollution and incident childhood asthma: the traffic, asthma and genetics (TAG) Study. Environ Health Perspect 122:418–424; http://dx.doi.org/10.1289/ehp.1307459     

Influence of Glutathione S-Transferase Polymorphisms on Cognitive Functioning Effects Induced by p,p′-DDT among Preschoolers

Background

Early-life exposure to p,p′-DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] is associated with a decrease in cognitive skills among preschoolers at 4 years of age. We hypothesized that genetic variability in glutathione S-transferase (GST) genes (GSTP1, GSTM1, and GSTT1) could influence the effects of prenatal exposure to p,p′-DDT.

Methods

We used data from 326 children assessed in a prospective population-based birth cohort at the age of 4 years. In that study, the McCarthy Scales of Children’s Abilities were administrated by psychologists, organochlorine compounds were measured in cord serum, and genotyping was conducted for the coding variant Ile105Val from GSTP1 and for null alleles from GSTM1 and GSTT1. We used linear regression models to measure the association between organochlorines and neurodevelopmental scores by GST polymorphisms.

Results

p,p′-DDT cord serum concentration was inversely associated with general cognitive, memory, quantitative, and verbal skills, as well as executive function and working memory, in children who had any GSTP1 Val-105 allele. GSTP1 polymorphisms and prenatal p,p′-DDT exposure showed a statistically significant interaction for general cognitive skills (p = 0.05), quantitative skills (p = 0.02), executive function (p = 0.01), and working memory (p = 0.02). There were no significant associations between p,p′-DDT and cognitive functioning at 4 years of age according to GSTM1 and GSTT1 polymorphisms.

Conclusions

Results indicate that children with GSTP1 Val-105 allele were at higher risk of the adverse cognitive functioning effects of prenatal p,p′-DDT exposure.     

Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast cancer risk

BACKGROUND: Cruciferous vegetables are the primary source of isothiocyanates and other glucosinolate derivatives that are known to induce phase II detoxifying enzymes, including glutathione S-transferases (GSTs). OBJECTIVE: We investigated the independent and combined effects of cruciferous vegetable intake and the GSTP1 Ile(105)Val genetic polymorphism on breast cancer risk. DESIGN: Analyses included 3035 cases and 3037 population controls who were participating in the Shanghai Breast Cancer Study and for whom diet and genetic data were complete (87% of cases and 85% of controls). RESULTS: With the use of multivariate logistic regression, the GSTP1 Val/Val genotype was significantly associated with greater breast cancer risk (OR = 1.50; 95% CI: 1.12, 1.99). The association was significantly greater in premenopausal women (OR = 1.69; 95% CI: 1.17, 2.43) than in postmenopausal women (OR = 1.20; 95% CI: 0.74, 1.92). Total cruciferous vegetable intake was not significantly associated with breast cancer risk, although subjects reporting greater turnip (P for trend < 0.001) and Chinese cabbage (P for trend = 0.049) intakes had a significantly lower postmenopausal breast cancer risk. Women with the GSTP1 Val/Val genotype and low cruciferous vegetable intake had a breast cancer risk 1.74-fold (95% CI: 1.13, 2.67) that of women with the Ile/Ile or Ile/Val genotype. This effect of low cruciferous vegetable intake and the Val/Val genotype was seen predominantly among premenopausal women (OR = 2.08; 95% CI = 1.20, 3.59). CONCLUSIONS: Cruciferous vegetable intake consistent with high isothiocyanate exposure may reduce breast cancer risk. Cruciferous vegetable intake also may ameliorate the effects of the GSTP1 genotype.     

ADRB2基因多态性与0～5岁儿童喘息相关研究

目的:探讨ADRB2基因rs1042713位点在0～5岁儿童的分布特征、位点多态性与临床易感性的关系。方法:病例组0～5岁喘息儿童115例,对照组118例纳入研究,留取其口腔上皮细胞提取DNA,用实时荧光定量PCR法对ADRB2基因rs1042713位点SNP进行基因分型、统计,分析位点多态性与临床易感性。结果:基因多态性特征与国内其他地区、日本等人群相近。病例组与对照组等位基因之间、基因型之间的分布差异无统计学意义(P>0.05),而喘息发作严重程度在基因型的分布差异具有统计学意义(P<0.05)。结论:该地区病例ADRB2基因rs1042713位点多态性与0～5岁儿童喘息性疾病的易感性不相关,该位点的改变非喘息性疾病的始动因素;但与病情的发作严重程度相关,纯合子G/G基因型可能是重症病例的危险易感因素。     

Respiratory syncytial virus infection and recurrent wheezing in Chilean infants: A genetic background?

Respiratory syncytial virus (RSV) infection has been associated to recurrent wheezing, but pathogenic mechanisms are unclear. Interleukin-4/Interleukin-13 (IL-4/IL-13) pathway is involved in both conditions. A common host genetic susceptibility may exist in patients whom RSV will trigger severe illness and those who develop recurrent wheezing.ObjectiveTo assess, by a candidate-gene approach, whether genetic polymorphisms in IL-4/IL-13 pathway are associated with RSV infection severity and its outcome in Chilean children.A cohort of 118 RSV-infected infants was analyzed and followed for one year. Severity of acute infection and later recurrent wheezing were characterized. Alleles and genotypes frequencies were determined for two SNP in each of the genes IL-4, IL-13 and IL-4Rα. Association tests and interaction analyses were performed.Enrollment included 60 moderate and 58 severe cases. Two SNP were found associated to severity during acute infection in IL-4Rα gene (Gln551Arg, Ile50Val). The follow up was completed in 71% of patients (84/118). Later recurrent wheezing was 54% in severe group, versus 31% in moderate cases (p = 0.035). In relation to outcome, allele Ile50 in IL-4Rα was more frequent in patients with moderate disease and no wheezing outcome. A common protector genotype is proposed for Chilean children: IL-4Rα Ile/Ile.ConclusionGenetic variations in the host are associated to infection severity and outcome. A common genetic background might be influencing both pathologies.     

Interactions between glutathione S-transferase P1, tumor necrosis factor, and traffic-related air pollution for development of childhood allergic disease

BACKGROUND: Air pollutants may induce airway inflammation and sensitization due to generation of reactive oxygen species. The genetic background to these mechanisms could be important effect modifiers. OBJECTIVE: Our goal was to assess interactions between exposure to air pollution and single nucleotide polymorphisms (SNPs) in the beta2-adrenergic receptor (ADRB2), glutathione S-transferase P1 (GSTP1), and tumor necrosis factor (TNF) genes for development of childhood allergic disease. METHODS: In a birth cohort originally of 4,089 children, we assessed air pollution from local traffic using nitrogen oxides (traffic NO(x)) as an indicator based on emission databases and dispersion modeling and estimated individual exposure through geocoding of home addresses. We measured peak expiratory flow rates and specific IgE for inhalant and food allergens at 4 years of age, and selected children with asthma symptoms up to 4 years of age (n = 542) and controls (n = 542) for genotyping. RESULTS: Interaction effects on allergic sensitization were indicated between several GSTP1 SNPs and traffic NO(x) exposure during the first year of life (p(nominal) < 0.001-0.06). Children with Ile105Val/Val105Val genotypes were at increased risk of sensitization to any allergen when exposed to elevated levels of traffic NO(x) (for a difference between the 5th and 95th percentile of exposure: odds ratio = 2.4; 95% confidence interval, 1.0-5.3). In children with TNF-308 GA/AA genotypes, the GSTP1-NO(x) interaction effect was even more pronounced. We observed no conclusive interaction effects for ADRB2. CONCLUSION: The effect of air pollution from traffic on childhood allergy appears to be modified by GSTP1 and TNF variants, supporting a role of genes controlling the antioxidative system and inflammatory response in allergy.     

硒蛋白单核苷酸多态性与幽门螺旋杆菌感染的关联性

目的 探讨硒蛋白S（selenoprotein S,SelS）rs34713741位点、硒蛋白P（selenoprotein P,Sepp1）rs7579位点单核苷酸多态性（single nucleotide polymorphisms,SNPs）与幽门螺旋杆菌（Helicobacter pylori,Hp）感染的关联性。方法 采用等位基因特异性PCR（allele - specific PCR,AS - PCR）技术检测195例Hp感染者和200例对照者SelS（rs34713741）、Sepp1（rs7579）SNPs,统计分析其与Hp感染的关系。结果 rs34713741位点SelS基因SNP与Hp感染存在关联（P＜0.05)。与C等位基因携带者相比,携带T等位基因者感染Hp风险增高1.578倍（OR = 1.578,95%CI:1.191～2.091）;与CC基因型者相比,CT和TT基因型者感染Hp风险均增高（OR = 1.890,95%CI:1.134～3.148;OR = 1.807,95%CI:1.140～2.864）;rs7579位点Sepp1基因SNP与Hp感染无关联（P＞0.05)。结论 SelS基因rs34713741位点T等位基因提高了Hp感染风险,是Hp感染遗传易感基因。     

Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val) Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico

Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG). This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val) has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val) by an allelic discrimination assay. Biochemical tests and a three-day food record were assessed. The Val/Val genotype carriers had a higher intake of total carbohydrates, fiber and servings of cereals and vegetables than the other genotype carriers. The Val/Val genotype conferred a higher risk for HTG than the Ile/Val and Ile/Ile genotypes (OR = 3.26, 95%CI 1.35–7.86, p = 0.006 and OR = 2.61, 95%CI 1.12–6.07, p = 0.02, respectively). Furthermore, the Val/Val genotype was associated with approximately 30% higher triglycerides compared with Ile/Val and Ile/Ile genotypes (β = 44.09, 95%CI 9.94–78.25, p = 0.01 and β = 45.7, 95%CI 10.85–80.54, p = 0.01, respectively). In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG.     

TRPV1 UTR-3基因多态性与北京汉族儿童哮喘的易感性研究

目的研究TRPV1 UTR-3基因多态性对北京汉族儿童哮喘易感性的影响。方法采用ISSAC统一问卷进行病例对照研究,从美国国家生物技术信息中心(NCBI)数据库选取TRPV1基因UTR-3区域rs58868916、rs9899485、rs4790521、rs4790522、rs402369及ENSSNP11193515作为目的SNP。通过PCR方法检测177名哮喘儿童、44名遗传性过敏症儿童及151名非哮喘对照儿童TRPV1基因多态性;通过Hardy-Weinberg平衡检验、卡方检验、连锁不平衡(LD)分析、Logistic回归分析和模型拟合,分析TRPV1基因SNP等位基因频率(MAF)、基因型及单倍型差异。结果Hardy-Weinberg平衡检验的P>0.05,满足基因型均衡要求;哮喘儿童与对照rs4790521T/C等位基因频率有显著差异(P<0.05);rs4790522A/C杂合子携带者哮喘患病风险显著低于纯合子A/A及C/C携带者(OR=0.588,95%CI=0.376～0.920,P<0.05),rs4790521隐性纯合子C/C携带者哮喘患病风险显著高于纯合子T/T及杂合子T/C携带者(OR=2.94,95%CI=1.32～6.53,P<0.01);LD分析显示rs4790521与rs4790522存在连锁不平衡(D’=0.959,r2=0.120),此2位点SNP构建出3个频率大于0.10的单倍型;通过Logistic逐步回归调整年龄、性别、家族遗传史及家庭成员吸烟等混杂因素后,rs4790521SNP的MAF、隐性纯合子C/C、及单倍型Hap2-C/C与儿童哮喘密切相关,是影响儿童哮喘易感性的重要危险因素,P值均小于0.05。结论TRPV1基因UTR-3多态性与中国北京汉族儿童哮喘易感性相关。     

GSTM1, GSTT1, and GSTP1 polymorphisms, breast cancer risk factors and mammographic density in women submitted to breast cancer screening

Genetic polymorphisms in genes related to the metabolism of xenobiotics, such as genes of the glutathione S-transferases (GSTM1, GSTT1, and GSTP1) superfamily have been associated with an increased risk for breast cancer (BC). Considering the high incidence of BC in the city of Porto Alegre in southern Brazil, the purpose of this study was to characterize genotypic and allelic frequencies of polymorphisms in GSTM1, GSTT1, and GSTP1, and correlate these molecular findings with established risk factors for breast cancer including mammographic density, in a sample of 750 asymptomatic women undergoing mammographic screening. Molecular tests were performed using the multiplex polymerase chain reaction (PCR) for GSTM1 and GSTT1, and quantitative PCR for GSTP1 polymorphisms. Overall, the frequencies of GSTM1 and GSTT1 null genotypes were 45% and 21%, respectively. For GSTP1 polymorphism, genotypic frequencies were 44% for the Ile/Ile genotype, 44% for the Ile/Val genotype, and 12% for Val/Val genotype, with an allelic frequency of 66% for the wild type allele in this population, similar to results of previous international publications. There was a statistically significant association between the combined GSTM1 and GSTT1 null genotypes (M-/T-) and mammographic density in post menopausal women (p = 0.031). When the GSTT1 null (T-) genotype was analyzed isolated, the association with mammographic density in post menopausal women and in the overall sample was also statistically significant (p = 0.023 and p = 0.027, respectively). These findings suggest an association of GSTM1 and GSTT1 null genotypes with mammographic density.     

Genetic variation in glutathione-related genes and body burden of methylmercury

BACKGROUND: Exposure to toxic methylmercury (MeHg) through fish consumption is a large problem worldwide, and it has led to governmental recommendations of reduced fish consumption and blacklisting of mercury-contaminated fish. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES: We conducted this study to assess the influence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modifier subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit (GCLC-129)] or GSH-conjugating [glutathione S-transferase pi 1 (GSTP1-105 and GSTP1-114)] genes on MeHg retention. METHODS: Based on information obtained from questionnaires, 292 subjects from northern Sweden had a high consumption of fish (lean/fat fish two to three times per week or more). We measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for fish intake). RESULTS: The GSTP1 genotype modified Ery-Hg; effects were seen for GSTP1-105 and -114 separately, and combining them resulted in stronger effects. We found evidence of effect modification: individuals with zero or one variant allele demonstrated a steeper regression slope for Ery-Hg (p=0.038) compared with individuals with two or more variant alleles. The GCLM-588 genotype also influenced Ery-Hg (p=0.035): Individuals with the GCLM-588 TT genotype demonstrated the highest Ery-Hg, but we saw no evidence of effect modification with increasing P-PUFA. CONCLUSIONS: These results suggest a role of GSH-related polymorphisms in MeHg metabolism.     

GSTT1 genotype modifies the association between cruciferous vegetable intake and the risk of myocardial infarction

BACKGROUND: Cruciferous vegetables are a major dietary source of isothiocyanates that may protect against coronary heart disease. Isothiocyanates induce glutathione S-transferases (GSTs), polymorphic genes that code for enzymes that conjugate isothiocyanates, as well as mutagens and reactive oxygen species, to make them more readily excretable. OBJECTIVE: The objective of the study was to determine whether GST genotypes modify the association between cruciferous vegetable intake and the risk of myocardial infarction (MI). DESIGN: Cases (n = 2042) with a first acute nonfatal MI and population-based controls (n = 2042) living in Costa Rica, who were matched for age, sex, and area of residence, were genotyped for a deletion polymorphism in GSTM1 and GSTT1 and an Ile105Val substitution in GSTP1. Cruciferous vegetable intake and smoking status were determined by questionnaire. Odds ratios (ORs) and 95% CIs for MI were estimated by unconditional logistic regression. RESULTS: Compared with the lowest tertile of cruciferous vegetable intake, the highest tertile was associated with a lower risk of MI among persons with the functional GSTT1*1 allele (OR: 0.70; 95% CI: 0.58, 0.84) but not among those with the GSTT1*0*0 genotype (OR: 1.23; 95% CI: 0.83, 1.82) (P = 0.006 for interaction). This protective effect among those with the GSTT1*1 allele was greater for current smokers (OR: 0.54; 95% CI: 0.36, 0.79) than for nonsmokers. GSTP1 and GSTM1 did not modify the association between cruciferous vegetable intake and MI. CONCLUSIONS: Consumption of cruciferous vegetables was associated with a lower risk of MI among those with a functional GSTT1*1 allele, which suggests that compounds that are detoxified by this enzyme contribute to the risk of MI.     

MPO、NQO1、GSTP1和UGT1A6基因多态与慢性苯中毒遗传易感性关系

目的探讨MPO、NQO1、GSTP1和UGT1A6基因多态与慢性苯中毒易感性的关系。方法采用病例-对照研究,以268名苯中毒工人为病例组,268名接触苯而没有中毒表现的工人为对照组。应用TaqManPCR分析技术判定MPO(rs7208693),NQO1(rs1800566),GSTP1(rs947894)和UGT1A6(rs6759892,rs1105879,rs4124874,rs3755319,rs887829和rs4148323)基因型。结果携带GSTP1基因rs947894G等位基因个体患慢性苯中毒的危险性比AA基因型个体降低0.657倍(95%CI0.434~0.994,P=0.046);携带MPO基因rs7208693A等位基因人群中,UGT1 A6 rs6759892G等位基因个体发生慢性苯中毒的危险性是TT基因型的2.702倍(P=0.024),UGT1 A6 rs1105879C等位基因个体发生慢性苯中毒的危险性是TT型的2.619倍(P=0.035)。在饮酒人群中,携带NQO1基因rs1800566TT基因型个体慢性苯中毒的发病风险较携带CC和CT基因型个体增加9.000倍(95%CI1.460~55.478,P=0.021);在吸烟人群中,带NQO1基因rs1800566TT基因型个体慢性苯中毒的发病风险较携带CC和CT基因型个体增加7.000倍(95%CI1.555~31.575,P=0.012)。单倍型分析显示,本人群携带UGT1A6基因TACGGG单倍型个体慢性苯中毒的发病风险是携带TAATGG单倍型个体的1.446倍(OR=1.446,95%CI1.005~2.080,P=0.046)。结论同时携带MPO基因rs7208693A和UGT1A6基因rs6759892G或rs1105879C等位基因型个体对苯中毒易感;携带NQO1基因rs1800566TT基因型且同时吸烟或饮酒的个体对苯中毒易感;携带UGT1A6基因TAATGG单倍型个体可增加慢性苯中毒的发病风险;GSTP1基因多态与慢性苯中毒遗传易感性的关系仍需进一步研究。     

Baseline determination in social, health, and genetic areas in communities affected by glyphosate aerial spraying on the northeastern Ecuadorian border

The northeastern Ecuadorian border has undergone aerial spraying with an herbicide mix that contains surfactants and adjuvants, executed by the Colombian Government. The purpose of this study was to diagnose social, health, and genetic aspects of the people affected by glyphosate. For this objective to be achieved, 144 people were interviewed, and 521 medical diagnoses and 182 peripheral blood samples were obtained. Genotyping of GSTP1 Ile105Val, GPX-1 Pro198Leu, and XRCC1 Arg399Gln polymorphisms were analyzed, using PCR-RFLP technique. The assessment of chromosomal aberrations was performed, obtaining 182 karyotypes. Malnutrition in children was 3%. Of the total population, 7.7% had children with malformations, and the percentage of abortions was 12.7%. Concerning genotyping, individuals with GSTP1 Val/Val obtained an odds ratio of 4.88 (p < 0.001), and Ile/Val individuals, together with Val/Val individuals, had an odds ratio of 2.6 (p < 0.05). In addition, GPX-1 Leu/Leu individuals presented an odds ratio (OR) of 8.5 (p < 0.05). Regarding karyotyping, the 182 individuals had normal karyotypes. In conclusion, the study population did not present significant chromosomal and DNA alterations. The most important social impact was fear. We recommend future prospective studies to assess the communities.     

Effect of polymorphic metabolizing genes on micronucleus frequencies among benzene-exposed shoe workers in China

It is well-known that metabolism of benzene is required for the induction of toxicity and consequent health problems. Therefore, genetic variation in benzene (BZ) metabolism genes can influence health outcomes. However, large population studies are needed to provide more evidence for such relationship. We have conducted a large population investigation (385 BZ-exposed shoe workers and 197 matched healthy controls) on the association between inheritance of certain BZ metabolizing genes and the expression of micronuclei (MN). The latter was based on the cytokinesis-blocked MN assay. We analyzed the polymorphisms of GSTM1, GSTT1, GSTP1 (rs1695), CYP2E1 (rs3813867), CYP2E1 (rs2031920), CYP2E1 (rs6413432), mEH exon 3 (rs1051740), mEH exon 4 (rs2234922). Univariate Poisson regression analysis demonstrated that the BZ-exposed workers had significantly increased MN frequency compared with the controls (FR = 1.84, 95% CI: 1.56–2.18; P < 0.001), and showed a cumulative exposure dose–response relationship. The CYP2E1 rs3813867 mutant allele (CC + GC) (FR 1.15, 95% CI 1.02–1.29; P = 0.020) and rs2031920 variant allele (CT + TT) (FR = 1.23, 95% CI: 1.09–1.37, P < 0.01) was associated with higher MN frequency significantly compared with the wild genotype separately. Furthermore, the MN frequency in rs2031920 variant allele (CT + TT) (FR = 1.17, 95% CI: 1.04–1.31, P < 0.01) was also higher than the wild genotype when the age, gender and cumulative exposure dose was adjusted in Poisson regression. In addition, the CYP2E1, however, GSTM1null, GSTT1null, GSTP1 rs1695, rs6413432, rs1051740 and rs2234922 polymorphisms showed no association with MN frequency. Our results indicate that two promoter polymorphisms in the CYP2E1 gene, especially the rs2031920 variant allele, were involved with the BZ-induction of MN and may contribute to risk of cancer among exposed workers.     

CYP1A1基因多态性和GSTM1缺失与肺癌易感性的关系

[目的]探讨CYPlAl基因异亮氨酸(Ile)-缬氨酸(Val)位点多态性和GSTMl缺失与肺癌易感性的关系。[方法]以病例-对照方法,采用PCR技术检测82例原发性肺癌患者和91例对照者的CYPlAl基因Ile-Val位点多态性与GSTMl基因的缺失。[结果]Ile-Val3种多态基因型在肺癌组和对照组分布差异有显著性(P<0.05),Ile／Val、Val／Val基因型在肺癌组的分布频率明显高于对照组;logistic回归分析结果显示Ile／Val、Val／Val基因型患肺癌的危险性分别是Ile／Ile基因型的1.969(95％CI:1.012-3.828)倍和3.150倍(95％CI:1.278-7.761);GSTMl基因缺失在两组的分布频率差异有显著性(P<0.05,OR=2.157)。进一步联合CYPlAl多态性分析显示GSTMl缺失的个体同时携带Ile／Val或Val／Val基因型患肺癌的危险性较单独具有一种危险因子患肺癌的危险性显著增加(OR=5.538)。[结论]CYPlAl第7外显子的Ile／Val、Val／Val基因型和GSTMl缺失与肺癌的易感性有关,可望作为肺癌易感人群筛选的重要指标。     

IL-6基因单核苷酸多态性与系统性红斑狼疮的相关性研究

目的探讨白细胞介素（interleukin,IL）6单核苷酸多态性（single nucleotide polymorphism,SNP）（rs1800796）与系统性红斑狼疮（systemic lupus erythematosus,SLE）的易感性。方法选取SLE患者666例作为病例组,年龄、性别匹配的569例正常人作为对照组,采用TaqMan基因分型技术检测rs1800796基因型频率。结果 Rs1800796 SNP的基因型（CC,CG和GG）频率和等位基因（C和G）频率在SLE患者和对照间差异均无统计学意义（均有P〉0.05）。Rs1800796与SLE临床表现的关联性分析发现,C等位基因频率在伴有浆膜炎的SLE患者中低于不伴有浆膜炎的SLE患者（P=0.019）。但C等位基因频率的分布在是否表现有颧部红斑、盘状红斑、光敏感、口腔溃疡、关节炎及狼疮肾炎的SLE病人间差异均无统计学意义（均有P〉0.05）。结论尚未发现IL-6rs1800796在中国汉族人群与SLE遗传易感性有关。Rs1800796 C等位基因可能对SLE病人并发浆膜炎起保护作用。