[Genetic susceptibility of DNA damage induced by vinyl chloride monomer exposure].

OBJECTIVE: To explore the association between DNA damage induced by vinyl chloride monomer (VCM) and polymorphisms of DNA repair genes and xenobiotic metabolism genes of VCM. METHODS: Comet assay was employed to detect DNA damage. Based on the status of DNA damage, the VCM exposure workers were divided into two groups: DNA damage group (75) and control group (75). Case-control design was used to investigate the association between the genetic polymorphisms and DNA damage induced by VCM. Genotypes of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), XPD (Ile199Met, Asp312Asn and Lys751Gln) and CYP2E1 were identified by the PCR-RFLP. PCR assay was used to detect positive and null genotype of GSTT1 and GSTM1. RESULTS: Univariate analysis showed that the CYP2E1 c1c2/c2c2 and XPD751 Lys/Gln and Gln/Gln genotypes were significantly associated with the increased levels of DNA damage, XRCCI 339 Arg/Gln and Gln/Gln genotypes were significantly associated with the decreased levels of DNA damage (P < 0.01, P < 0.05, respectively). Logistic regression analysis showed that there was significant association between the genotypes of XRCC1 194, XRCC1 399, XPD 751, CYP2E1 and DNA damages. A prominent risk decreasing of DNA damage was observed for those individuals possessing XRCC1 399Arg/Gln + Gln/Gln genotypes (OR: 0.35, 95%CI: 0.12 approximately 1.01, respectively); The results also showed that there were significant associations between CYP2E1 c1c2/c2c2 and DNA damage both in high and low VCM-exposed groups (OR: 2.57, 95%CI: 1.01 approximately 6.59 and OR: 2.57, 95%CI: 0.99 approximately 6.87). CONCLUSION: Cumulative exposure dose and genotypes of XRCC1 194, XRCC1 399, XPD 751 and CYP2E1 may modulate the DNA damage induced by VCM exposure.

CYP2E1 mRNA expression, genetic polymorphisms in peripheral blood lymphocytes and liver abnormalities in Chinese VCM-exposed workers.

OBJECTIVE: To study the relationship between expression of cytochrome P4502E1 (CYP2E1) in human lymphocytes, variant CYP2E1 genotype, exposure to vinyl chloride monomer (VCM), and liver abnormalities in VCM-exposed workers. METHODS: A case-control study was performed on 90 male occupationally exposed workers and 42 matched male nonexposed controls. Data were collected based on health surveillance, workplace investigation and questionnaire Survey. Total RNA and DNA were isolated from peripheral blood lymphocytes, and CYP2E1 mRNA expression was determined using RT-PCR, and the presence of CYP2E1 polymorphisms was identified based on PCR-RFLP. RESULTS: The mRNA expression of CYP2E1 in exposed workers (0.89+/-0.46) was significantly higher than in nonexposed controls (0.61+/-0.35) (P < 0.01). Logistic regression analysis demonstrated a statistically significant association between CYP2E1 mRNA expression levels and liver abnormalities in the VCM-exposed workers (OR = 3.66, P < 0.05). The genotype frequency for CYP2E1 variants among VCM-exposed workers was not significantly different between workers with liver abnormalities and those without. CONCLUSIONS: Liver abnormalities in subjects exposed to VCM are positively associated with expression of peripheral blood lymphocyte mRNA, which is significantly increased in exposed workers compared to nonexposed controls. Therefore, CYP2E1 mRNA levels may be useful for health surveillance and protection of VCM-exposed workers.

[Polymorphisms of FAS and FASL genes and susceptibility of silicosis].

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.

[Relationship between single nucleotide polymorphisms of NRAMP1 gene and susceptibility to pulmonary tuberculosis in workers exposed to silica dusts].

OBJECTIVE: To explore the relationship between polymorphisms of natural resistance-associated macrophage protein 1 (NRAMP1) gene and genetic susceptibility of pulmonary tuberculosis (PTB) in workers exposed to silica dusts. METHODS: A 1:2 case control study of 61 male workers with PTB (50 silicosis patients and 11 unsilicosis workers) as the case group and 122 male PTB-free workers (100 silicosis patients and 22 unsilicosis workers) as the control group was conducted with the frequency matched for age of +/- 5 years, the job, the silica exposure, and the condition of cigarette smoking and alcohol drinking. The polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was used to detect the single nucleotide polymorphisms (SNPs) of NRAMP1 INT4 and D543N. RESULTS: There was a 2.73 times (95% CI: 1.32 approximately 5.64) increased risk of silicosis for individuals with C allele of NRAMP1 INT4 compared with individuals carrying homozygote (G/G), while SNPs of NRAMP1 D543N was not associated with PTB (P > 0.05). CONCLUSION: The G > C mutation of intron 4 of NRAMP1 gene might be a susceptible factor of silica for the workers exposed to PTB.