RESUMO
OBJECTIVE: To explore the association of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning (CBP) comprehensively by case-control design. METHODS: 152 CBP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. 30 single nucleotide polymorphisms (SNPs) in 13 genes such as CYP2E1 were tested by PCR-RFLP, sequencing approaches. Logistic regression model was used to detect main effects and 2-order interaction effects of gene and/or environment. Multifactor dimensionality reduction (MDR) was used to detect high-order gene-gene or gene-environment interactions. RESULTS: Based on logistic regression, the main effects of GSTP1 rs947894, EPHX1 rs1051740, CYP1A1 rs4646903, CYP2D6 rs1065852 and rs1135840 were found to be significant (P < 0.05) while the confounding factors of sex, cigarette smoking, alcohol consumption and the intensity of benzene exposure were controlled. EPHX1 rs1051740 might be associated with CBP (P = 0.06). There existed 3 types of interactions were as followed: interactions of GSTP1 rs947894 with alcohol consumption, CYP2E1 rs3813867 with EPHX1 rs3738047, EPHX1 rs3738047 with alcohol consumption(P < 0.05), while the main effects of CYP2E1 rs3813867 and EPHX1 rs3738047 were not significant (P > 0.05). The other SNPs did not show any significant associations with CBP. According to MDR, a 3-order interaction with the strongest combined effect was found, i.e. the 3-factor combination of CYP1A1 rs4646903, CYP2D6 rs1065852 and CYP2D6 rs1135840. CONCLUSION: Gene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.
Assuntos
Benzeno/intoxicação , Citocromo P-450 CYP2E1/genética , Exposição Ocupacional , Adulto , Estudos de Casos e Controles , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP2D6/genética , Epóxido Hidrolases/genética , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redução Dimensional com Múltiplos Fatores , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Vinyl chloride (VC) was classified as a group 1 carcinogen by IARC in 1987. Although the relationship between VC exposure and liver cancer has been established, the mechanism of VC-related carcinogenesis remains largely unknown. Previous epidemiological studies have shown that VC exposure is associated with increased genotoxicity in humans. To explore chromosomal damage and its progression, and their association to genetic susceptibility, we investigated 402 workers exposed to VC, a 77 VC-exposed cohort and 141 unexposed subjects. We measured the frequencies of cytokinesis-block micronucleus (CBMN) to reflect chromosomal damage and conducted genotyping for six xenobiotic metabolisms and five DNA repair genes' polymorphism. Data indicate that 95% of the control workers had CBMN frequencies =3 per thousand, whereas VC-exposed workers had the 3.73-fold increase compared with the controls. Among the cohort workers who were followed from 2004 to 2007, the mean CBMN frequency was higher in 2007 than in 2004 with ratio of 2.08. Multiple Poisson regression analysis showed that mean CBMN frequencies were significantly elevated for the intermediate and high exposure groups than the low. Exposed workers with CYP2E1 or XRCC1 variance showed a higher CBMN frequency than their wild-type homozygous counterparts, so did workers with GSTP1 or ALDH2 genotype. This study provides evidence that cumulative exposure dose of VC and common genetic variants in genes relevant to detoxification of carcinogens are the major factors that modulate CBMN induction in VC-exposed workers.
Assuntos
Cromossomos/efeitos dos fármacos , Reparo do DNA , Predisposição Genética para Doença , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Exposição Ocupacional , Adulto , Povo Asiático/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição de Poisson , Fatores de Tempo , Cloreto de Vinil/toxicidadeRESUMO
OBJECTIVE: To probe into the application of fuzzy cluster in analysis of therapeutic effects of electro-acupuncture at different parameters on adjuvant-induced arthritis (AA) in rats. METHODS: One hundred Wistar rats were randomly divided into ten groups: normal control group, untreated group and eight electro-acupuncture groups at different parameters. There were ten rats in each group. AA rats were treated by electro-acupuncture at different frequencies (2 Hz or 100 Hz), waveforms (successive wave or intermittent wave) and current intensities (0.1 mA or 0.2 mA). Firstly, the anti-inflammatory and analgesic effects of electro-acupuncture at different parameters were compared with orthogonal experiment, and then with the application of fuzzy mathematics, the data of joint swelling, pain threshold and the contents of beta-endorphin (beta-EP) and interleukin-1beta (IL-1beta) after the treatment in all groups were standardized by the method of data range normalization. Programming and solution were done by MATLAB. The methods of fuzzy similar matrix and the transitive closure were used in similarity evaluation of therapeutic effects of electro-acupuncture at different parameters. RESULTS: Based on index determination and variance analysis, both the normal control group and untreated group were clustered to one category as lambda equaled to 0.72. Electro-acupuncture at 100 Hz, successive wave, 0.2 mA, electro-acupuncture at 100 Hz, intermittent wave, 0.1 mA and electro-acupuncture at 100 Hz, intermittent wave, 0.2 mA were clustered to one category and had similar good anti-inflammatory and analgesic effects. The therapeutic effects of the remaining electro-acupuncture types were similar. CONCLUSION: Fuzzy cluster analysis provides a better method for evaluating the overall therapeutic effects of electro-acupuncture with multiple factors.
Assuntos
Artrite Experimental/terapia , Análise por Conglomerados , Eletroacupuntura , Lógica Fuzzy , Animais , Feminino , Limiar da Dor , Distribuição Aleatória , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the relationship between polymorphisms of FAS and FASL genes and genetic susceptibility of silicosis. METHODS: A case-control study was conducted. The case group was 183 male patients with silicosis and the control group was 111 male silica-exposed but without silicosis miners. Data on total dust concentrations was collected to estimate cumulative total dust exposure (CTE) of each subject and each person's characteristics and work history were obtained from questionnaire. Polymerase chain reaction re-strained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) of FAS-1377, FAS-670 and FASL-844. Associations between polymorphisms and risk of silicosis and stages, interactions between polymorphisms, between polymorphisms and CTE and smoking and haplotypes were analyzed. RESULTS: There were no differences in the FAS-1377, FAS-670 and FASL-844 genotypes between the case group and the control group (P > 0.05). No association was observed between FAS-1377, FAS-670 and FASL-844 polymorphisms and silicosis and stages (P > 0.05). The frequencies of FAS-1377G/-670G haplotype in the cases (9.6%) were higher than those in the controls (3.6%) (P < 0.05). No interactions between the polymorphisms of different genes, the gene polymorphism and the total accumulative total dust, the gene polymorphism and smoking were observed (P > 0.05). CONCLUSION: FAS-1377, FAS-670 and FASL-844 polymorphisms are not susceptible factors of silicosis. The FAS-1377G/-670G haplotype might be a susceptibility marker of silicosis.
Assuntos
Proteína Ligante Fas/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Silicose/genética , Receptor fas/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de RestriçãoRESUMO
OBJECTIVE: To introduce the method of analyzing repeated data measured by water maze with SPSS 11.0, and offer a reference statistical method to clinical and basic medicine researchers who take the design of repeated measures. METHODS: Using repeated measures and multivariate analysis of variance (ANOVA) process of the general linear model in SPSS and giving comparison among different groups and different measure time pairwise. RESULTS: Firstly, Mauchly's test of sphericity should be used to judge whether there were relations among the repeatedly measured data. If any (PAssuntos
Computação Matemática
, Aprendizagem em Labirinto/fisiologia
, Modelos Estatísticos
, Análise de Variância
, Animais
, Modelos Lineares
, Masculino
, Memória/fisiologia
, Ratos
, Ratos Sprague-Dawley
, Fatores de Tempo