Genetic polymorphisms of IL-1A, IL-1B, IL-1RN, NFKB1, FAS, and FASL, and risk of silicosis in a Chinese occupational population.

OBJECTIVE: To test whether polymorphisms in IL-1, NF-KB, FAS, and FASL genes are associated with risk of silicosis. METHODS: A case-control study was conducted with 183 silicosis patients and 111 silica-exposed miners who were frequency-matched by age, dust exposure duration, work location, and type of work. Genotype analysis was performed on genomic DNA, using a PCR-RFLP assay. RESULTS: Individuals carrying the NFKB1 ins/del genotype had a decreased risk of silicosis (adjusted OR = 0.57, 95% CI = 0.32-0.998, P = 0.049) compared with subjects carrying the ins/ins genotype and individuals with the FAS-1377AA homozygote had a decreased risk of silicosis compared with those with the -1377GG genotype (adjusted OR = 0.42, 95% CI = 0.19-0.93, P = 0.03). The analysis of haplotypes of polymorphisms in FAS showed that there was a 2.71-fold (OR = 2.71, 95% CI = 1.22-6.03, P = 0.011) increased risk of silicosis for subjects with alleles of FAS-1377G and FAS-670G, compared with those carrying alleles of FAS-1377G and FAS-670A. CONCLUSION: Although the polymorphisms at NFKB1, FAS-1377, and extended haplotype FAS-1377G/-670G may play a role in the development of silicosis in the Chinese population, our findings should be verified by larger studies with >1 case/control ratio.

Genetic polymorphisms in alveolar macrophage response-related genes, and risk of silicosis and pulmonary tuberculosis in Chinese iron miners.

Alveolar macrophages (AMs) play a prominent role in influencing the development of lung inflammation and injury. The aim of this study is to investigate the roles of AMs response-related genes TNF-alpha, iNOS, and NRAMP1 (SLC11A1) in susceptibility to silicosis and pulmonary tuberculosis (PTB), and to analyze the interaction of dust exposure and genetic susceptibility to silicosis, interactions of TNF-alpha-308 and Natural Resistance-associated Macrophage Protein 1 (NRAMP1) INT4, D543N polymorphisms to PTB. Several epidemiological designs were used: retrospective investigations on dust exposure, case-control studies of 184 silicosis cases and 111 miners occupationally exposed to silica dust, and 1:2 matched case-control studies of 61 PTB cases and 122 PTB-free miners. The miners and controls were recruited from an iron mining operation in Anhui province, China. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was applied to detect single nucleotide polymorphisms. Despite the recruitment of high dust exposure among the controls, silicosis patients still had significantly higher dust exposure than controls (242.6 +/- 98.8 vs. 217.6 +/- 100.7 mg a/m(3)). The mutation of iNOS Ser608Leu is associated with protection against silicosis and against severity of silicosis in the miners. There is a 0.47-fold (95% CI: 0.28-0.79) decrease in risk of silicosis for individuals with C/T, T/T genotype compared with the wild-type homozygous (C/C) individuals after adjustment for occupational exposure, smoking, and drinking. The protection effect of the iNOS polymorphism was particularly detected in the > or = 150 mg a/m(3) exposure group (OR: 0.44, 95% CI: 0.22-0.91). However, no interaction of dust exposure with the iNOS polymorphism was observed. Furthermore, the variant NRAMP1 INT4 genotype is significantly associated with PTB in miners. No association of other polymorphisms (NRAMP1 D543N, TNF-alpha-308) and susceptibility to silicosis or PTB in Chinese miners was found. Our data showed a 3.26-fold (95% CI: 1.47-7.23) increased risk of PTB for miners carrying both the NRAMP1 D543N G/G and NRAMP1 INT4 G/C+C/C genotypes. Additionally, in miners with TNF-alpha-308 G/G genotype, the risk of PTB increased 2.38-fold if they carry the NRAMP1 INT4 G/C+C/C genotype (95% CI: 1.14-4.98). In conclusion, the C>T mutation of iNOS Ser608Leu may be an important protective factor to miners. On the other hand, the variant NRAMP1 INT4 may play a role in the development of PTB in Chinese miners. Therefore, the novel information can be used as guideline for further mechanistic investigations and for strengthening specific protection protocols for workers.

[Genetic polymorphism of CYP-1A1, CYP2D6 and risks of chronic benzene poisoning].

OBJECTIVE: To explore the relationship between genetic polymorphisms of CYP-1A1 and CYP2D6 and risks of chronic benzene poisoning (BP). METHODS: A case control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were involved. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technology was used for detecting the single nucleotide polymorphisms (SNPs) of MspI in the non-coding region of CYP-1A1 gene and c.188, g.212 position in the first extron of CYP2D6 gene. RESULTS: The individuals with CYP1A1 MspI T/T genotype had a 1.32 times (95% CI: 1.05 approximately 1.65, P = 0.02) increased risk of BP compared with those carrying T/C and C/C genotypes. In no-smoking population, there was a 1.56 times (95% CI: 1.15 approximately 2.12, P = 0.003) increased risk of BP for subjects carrying CYP1A1 MspIT/T genotype compared with those carrying T/C and C/C genotypes. The individuals carrying CYP2D6 c.188 C/C or C/T genotype had a 1.23 times (95% CI: 1.05 approximately 1.42, P = 0.01) increased risk compared with those carrying T/T genotypes. In no-smoking population, there was a 1.23 times (95% CI: 1.04 approximately 1.47, P = 0.01) increased risk of BP for subjects carrying CYP2D6 c.188 C/C or C/T genotypes compared with those carrying T/T genotype. The single nucleotide polymorphism of g.212 position in the first extron of CYP2D6 gene had not been validated. CONCLUSION: The individuals with CYP2D6 c.188 C/C, CYP2D6 c.188 C/T and CYP1A1 MspIT/T genotypes tend to be more susceptible to benzene toxicity.

[Relation of genetic polymorphism of XRCC1 with risks of chronic benzene poisoning].

OBJECTIVE: To explore the relation between genetic polymorphisms in XRCC1 and risks of chronic benzene poisoning (BP). METHODS: A case-control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. PCR-RFLP was applied to detect the single nucleotide polymorphisms (SNPs) on c.194, c.280 and c.399 of XRCC1 gene. RESULTS: The proportion of XRCC1 c.194Arg/Trp + Trp/Trp genotypes in the case group was lower than that of the control group, while there was a higher proportion for XRCC1 C.280Arg/His + His/His in the case group. There was a 1.67-fold decreased risk of BP for individuals carrying XRCC1 C.194Arg/Trp + Trp/Trp genotypes (OR adj = 0.60, 95% CI: 0.37-0.97, P = 0.039) compared with subjects carrying Arg/Arg allele, and individuals carrying genotypes of XRCC1 C.280Arg/His + His/His had a 1.91-fold increased risk of BP compared with these carrying the wild allele (OR adj = 1.91, 95% CI: 1.17-3.10, P = 0.009). CONCLUSION: The risk of BP for subjects carrying XRCC1 c.194Arg/Trp + Trp/Trp genotypes may decrease while for individuals carrying XRCC1 c.280Arg/His + His/His genotypes may increase.

[Investigation on the association of safety perception and safety behaviors with occupational injuries in steel-workers].

OBJECTIVE: To explore the association of occupational injuries, with their individual safety perception and safety behaviors in steel workers, so as to provide basis for preventing and controlling occupational injuries. METHODS: Case-control design was used to compare the difference in safety perception and safety behaviors between the injury group and the control, and also to compare the difference in safety behaviors between different safety perception groups. RESULTS: There were remarkable differences in attitude toward the safety degree of the work (chi(2) = 5.444, P < 0.05), and accidents happening (chi(2) = 4.552, P < 0.05) between case group and control group. There were remarkable difference in safety behaviors including manual operations instead of facilities (chi(2) = 10.015, P < 0.01), cleaning up, examining or adjusting machine during work (chi(2) = 7.351, P < 0.05), attention diversion (chi(2) = 10.937, P < 0.01) and unsafe wearing (chi(2) = 7.521, P < 0.05) between case group and control group. There were also significant differences in many safety behaviors between those who thought the job was safe or unsafe. CONCLUSION: There is some association of occupational injuries with safety perception and safety behaviors. To reduce the occurrence of occupational injury, measures should been focused on strengthening safety management and controlling unsafe behaviors.

[Relation of genetic polymorphism of NQO1 and GSTT1 with risks of chronic benzene poisoning].

OBJECTIVE: To explore the relation between genetic polymorphisms of NQO1, GSTT1 and risks of chronic benzene poisoning (BP). METHODS: A case-control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. Polymerase chain reaction (PCR), denaturing high-performance liquid chromatography(DHPLC) and sequencing were used to detect the single nucleotide polymorphisms(SNPs) of the promoter and complete coding-region of NQO1 gene. Multiple PCR was used to detect GSTT1 genotype. RESULTS: In smoking population, there was 7.73-fold (95% CI: 1.71-34.97, P = 0.010) of risk in BP subjects carrying NQO1c. 609 T/T genotype, compared with those carrying C/C and C/T. genotype. In drinking population, the individuals carrying the 6th extron of NQO1c. 609 T/T homozygote genotype had a 11.00-fold(95% CI: 1.89-63.83, P = 0.005) risk of BP compared to those with NQO1c. 609 C/T and C/C genotypes. CONCLUSION: The subjects carrying NQO1c. 609 T/T genotype and together with the habit of smoking or drinking may be more susceptible to BP.

Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners.

Silicosis is a fibrotic lung disease produced by the inhalation and deposition of silica dust. The association between silicosis and pulmonary tuberculosis (PTB) has been well established. Cytokines participate in the development and progression of silicosis and PTB. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at position -308; in the transforming growth factor-beta 1 (TGF-beta1) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1,082, -819 and -592; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with silicosis and PTB. We conducted a case-control study with 183 silicosis patients and 111 silica-exposed miners, and a 1:2 matched case-control study of 61 PTB cases and 122 PTB-free miners. Genotype analysis was performed on genomic DNA, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. There was complete linkage disequilibrium (LD) between the -819C and -592C alleles of the IL-10 gene. The genotype frequencies were similar between cases and control subjects for all investigated cytokine polymorphisms (p>0.05). We did not find an association between the different genotypes and severity of silicosis. We assume that these genetic variants do not play a dominant role in silicosis and PTB in our Chinese population.