Associations of polymorphism of P22(phox) C242T, plasma levels of vitamin E, and smoking with coronary heart disease in China.

BACKGROUND: The C242T polymorphisms of P22(phox) and plasma vitamin E have been associated with the risk of coronary heart disease (CHD) in several studies, but the results have been inconsistent. In this study, we sought to examine potential interactions between P22(phox) genotypes, plasma vitamin E concentrations, and smoking in relation to CHD risk. METHODS: We determined C242T genotype frequency in the P22(phox) gene and plasma levels of vitamin E in 565 Chinese patients with CHD and 609 control subjects. Logistic regression was used to control for potential confounders in multivariate analyses. RESULTS: Compared with subjects with a CC genotype, subjects with a CT or TT genotype had a lower risk of CHD (multivariate-adjusted odds ratio [OR] 0.45, 95% CI 0.28-0.74, P = .001). Plasma concentrations of vitamin E were lower in case patients than in control subjects (multivariate-adjusted OR 0.65, 95% CI 0.50-0.86, P = .025). Compared with nonsmokers with a CC genotype, nonsmokers with a CT or TT genotype had a decreased risk of CHD (OR 0.25, 95% CI 0.12-0.53), but smokers with a CT or TT genotype had an increased risk (OR 2.04, 95% CI 0.74-5.61, P for interaction = .039). Smokers with a lower vitamin E concentration had a >3.0-fold greater risk of CHD than did nonsmokers with a higher vitamin E concentration (OR 3.52, 95% CI 2.36-5.24, P for interaction = .041). CONCLUSIONS: These data provide evidence that P22(phox) genotypes are significantly associated with CHD risk in a Chinese population and suggest potential interactions among smoking, P22(phox) genotypes, and vitamin E in relation to CHD risk.

[Relationship between GSTM1 and GSTT1 gene polymorphisms and noise induced hearing loss in Chinese workers].

OBJECTIVE: To investigate the relationship of GSTM1 and GSTT1 gene polymorphisms with the development of noise induced hearing loss (NIHL) in Chinese workers. METHODS: 194 workers exposed to occupational noise were drawn as the subjects in the cross-sectional epidemiological study. According to the result of audiometry, they were divided into two groups: the NIHL group and the normal group. The GSTM1 and GSTT1 genotypes of 93 workers with NIHL and 101 normal workers were tested by multiplex polymerase chain reaction. Results The study showed that there were no significant differences in the distribution of GSTM1 and GST1 existed/null genotypes frequencies between NIHL group and normal group (P > 0.05). After adjusted for age, sex, smoking, history of explosive noise exposure and cumulative noise exposure (CNE) with multiple logistic regression analysis, the risk of GSTT1 null group was found significantly higher than that of the GSTT1 non-null group (P < 0.05), the adjusted OR value of which was 1.952 (95% confidence interval 1.017 - 3.746). There was no significant difference between the GSTM1 null group and the GSTM1 non-null group in the risk of NIHL (P > 0.05). CONCLUSION: The results suggested that genetic polymorphism in GSTTI1 gene might play an important role in the development of NIHL in Chinese workers; the individuals with the GSTT1 null genotype might be more susceptible to NIHL.

[The influence of occupational exposure and smoking on lung ventilation of coke oven workers].

OBJECTIVE: To study the influence of occupational exposure and smoking on lung ventilation function of coke oven workers. METHODS: Environmental monitoring was performed on the top, side and bottom of some coke ovens. Lung ventilation function test was performed in 234 coke oven workers. RESULTS: The poison concentration in environment had such tendency as it was the highest on the top, then the side, and the lowest at the bottom. The standardized forced expiratory volume in the 1st second (FEV(1), 90.8% +/- 8.6%) and forced expiratory rate (FEV(1)%, 95.4% +/- 12.4%) of those coke oven workers who smoked were significantly lower than those non-smoking workers (100.9% +/- 14.3%, 108.9% +/- 17.6%); among those smoking workers, the partial correlation coefficients between forced vital capacity (FVC) and benzene soluble, benzopyrene, and smoking index were -0.249, -0.187 and -0.368 respectively; and the coefficients between FEV(1) and the three aspects were -0.255, -0.191 and -0.388; and the coefficients between FEV(1)% and them were -0.131, -0.107 and -0.065. Among those non-smoking workers, the coefficients between benzene solubles and FVC, FEV(1) and FEV(1)% were -0.154, -0.052 and -0.176, and between benzopyrene and them were -0.121, -0.037 and -0.159. CONCLUSION: The lung ventilation function of coke oven workers has certain negative correlation with both occupational exposure and smoking.

[Glutathione S-transferase M1, T1 genotypes and the risk of mountain sickness].

OBJECTIVE: To explore the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, T1 and susceptibility to mountain sickness. METHODS: Forty-three soldiers with acute mountain sickness and 80 healthy soldiers matching with sex/age and training under the same condition were divided into case group and control group. A multiple polymerase chain reaction method was used to detect GSTM1 and GSTT1 genes in genomic DNA isolated from peripheral blood cells from both cases and controls. RESULTS: The frequency of the GSTT1 positive genotype was significantly higher in cases (69.8%) than in controls (42.5%) (P = 0.004, OR = 3.12, 95% CI 1.42 approximately 6.86). The frequency of GSTM1 negative genotype was also higher in cases (72.1%) than in controls (52.5%) (P = 0.03, OR = 2.34, 95% CI 1.05 approximately 5.02). Persons with both GSTM1 and GSTT1 negative genotypes had 5-fold more risk than those with GSTT1 negative and GSTM1 positive genotypes in developing mountain sickness (OR = 5.04, 95% CI: 1.00 approximately 25.3). CONCLUSION: Genetic polymorphisms of glutathione S-transferase M1, T1 may be the risk factors in the development of mountain sickness.

[Role of heat shock protein 70 expression in DNA damage induced by benzo(a)pyrene].

OBJECTIVE: To explore heat shock protein 70 (HSP70) expression of A549 cells and its role in DNA damage caused by benzo(a)pyrene (BaP). METHODS: Human adenocarcinoma A549 cells were cultured in vitro, exposed by different concentrations of BaP (0, 1.25, 2.50, 5.00, 10.00 micro mol/L) for 6 hours, or 10 micro mol/L of BaP for different time (0, 4, 8, 12, 16, 24 and 48 h). Then HSP70 expression and DNA damage were detected using Western-blot and single cell gel electrophoresis (SCGE) assay respectively, and the relationship between HSP70 expression and DNA damage was further analyzed. RESULTS: The integral optical densities of HSP70 in A549 cells treated with 1.25, 2.50, 5.00 and 10.00 micro mol/L BaP for 6 h (49.63 +/- 1.30, 45.72 +/- 1.03, 40.53 +/- 0.95, 37.50 +/- 1.20 respectively) were lower than that of the control cells (59.43 +/- 1.17) (P < 0.05). When A549 cells were exposed to 10 micro mol/L BaP for 4, 8, 12, 16 h, the integral optical densities of HSP70 were 33.33 +/- 0.80, 29.23 +/- 0.91, 12.51 +/- 0.96, 9.50 +/- 1.25 respectively, and there was an increasing tendency of the expression of HSP70 for 24 - 48 h (20.06 +/- 1.38, 24.51 +/- 1.39), however, all were different from that in control group (56.59 +/- 0.85) (P < 0.05). DNA damage scores in 10(6) A549 cells treated with 2.50, 5.00 and 10.00 micro mol/L BaP for 6 h (23,718 +/- 2,938, 30,128 +/- 2,937, 44,231 +/- 3,846) were significantly higher than that of the control cell (9,615 +/- 1,923) (P < 0.05). When A549 cells were exposed to 10 micro mol/L BaP for 4, 8, 12, 16, 24, 48 h, DNA damage scores (16,667 +/- 4,003, 38,461 +/- 1,924, 5,615 +/- 3,847, 76,282 +/- 2,937, 7,513 +/- 1,110 and 58,975 +/- 9,487) were also higher than that of control group (P < 0.05). There was a negative correlation between DNA damage and the expression of HSP70 when A549 cells were exposed to different concentrations of BaP. CONCLUSION: HSP70 might enhance intracellular defenses against DNA damage induced by BaP.

[Effects of mitogen activated protein kinase signal transduction pathways on heat shock protein 70 gene expression in endothelial cells exposed to benzo(a)pryene].

OBJECTIVE: To investigate the effects of mitogen activated protein kinase (MAPK) signal transduction pathways on heat shock protein 70 (HSP70) gene expression in endothelial cells exposed to benzo(a)pryene (BaP). METHODS: Porcine aortic endothelial cells were pre-treated or by PD98059 (10 micro mol/L) or SB203580 (20 micro mol/L) for 1 hour, then treated with different concentrations of BaP (0, 0.1, 0.5, 1.0, 5.0 and 10.0 micro mol/L) for 24 hours respectively;Expression levels of three phosphorylated MAPKs [extracellular signal regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38] and HSP70 were determined by Western-blot. RESULTS: The three phosphorylated MAPKs expressional levels especially p-ERK1 had different extents of changes with dose-response relationship under BaP exposure. BaP inhibited the expression of HSP70, which significantly decreased in medium and high dose group (>or= 1.0 micro mol/L) but did not decrease in control group (P < 0.05). Although the inhibitor of ERK (PD98059) could partly weaken the inhibited effects of BaP on HSP70 expression, HSP70 expression levels of endothelial cells pre-treated with PD98059 were still significantly lower than that of control cells (P < 0.05). CONCLUSION: ERK1 pathway might play some roles in HSP70 gene expression in endothelial cells exposed to BaP, and other unknown signal pathways might also have some effects on this process.

[Relationship of plasma nitric oxide concentration and the activity of nitric oxide synthase with coronary heart disease].

OBJECTIVE: To study the levels of nitric oxide synthase (NOS) and nitric oxide (NO) in patients with coronary heart disease (CHD), and the factors affecting them. METHODS: Concentrations of NO and the activities of NOS in plasma in 136 patients and 206 controls using the corresponding Kits were measured. The data were analyzed using covariance and multiple linear regression analysis with SAS 8.1. RESULTS: The levels of NO [(217.05 +/- 153.31) micromol/L] and NOS [(14.09 +/- 7.14) U/ml] in patients were significantly higher than that in the healthy controls [(140.69 +/- 90.96) micromol/L, (7.75 +/- 3.79) U/ml, respectively, P < 0.01]. Smoking and drinking were the independent risk factors for NOS, while sex was the independent risk factor for NO (P < 0.01). CONCLUSIONS: The levels of plasma NO and NOS are closely related with coronary heart disease.

[The expression of cytochrome P450 1A1 of endothelial cells induced by benzo(a)pyrene].

OBJECTIVE: To explore the effect of benzo(a)pyrene (BaP) on the expression and the activities of cytochrome P450 1A1 (CYP1A1) of porcine aortic endothelial cells. METHODS: Porcine aortic endothelial cells were cultured in vitro, and treated with different concentrations of BaP (0, 0.5, 1.0, 5.0, 10.0 micro mol/L) for 24 hours, CYP1A1 expression was determined by Western blot and immunohistochemistry. At the same time, the ethoxyresorufin-o-deethylase (EROD) activities were measured by spectrofluorometer. RESULTS: By Western blot, the expression of CYP1A1 of control cells was not found, but the expression of CYP1A1 of cells treated with BaP was found; By immunohistochemistry, only part of endothelial cells treated with BaP had positive expression of CYP1A1. The peak activities of EROD induced by BaP was at the concentration of 0.5 - 1.0 micro mol/L. CONCLUSION: BaP could induce part of endothelial cells to synthesize CYP1A1. BaP of 0.5 - 1.0 micro mol/L could induce peak activities of EROD.

[Relationship between heat stress protein 70 gene polymorphisms and the risk of acute mountain sickness].

OBJECTIVE: To investigate the relationship between heat stress proteins 70 (HSPs70) gene polymorphism and the risk of acute mountain sickness. METHODS: Fifty-six soldiers with acute mountain sickness and 173 soldiers without that were chosen as cases and controls. HSP70-1, HSP70-2 genotypes were analyzed by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: The HSP70-1 polymorphism was similar in two groups. The genotype frequency of HSP70-2 B/B in acute mountain sickness group (23.2%) was significantly higher than that in the control (6.9%, P < 0.05, OR = 4.02). CONCLUSION: There is a significantly increased association of HSP70-2 B/B genotype with the risk of acute mountain sickness. Individuals with HSP70-2 B/B genotype may have weaker adaptive ability than those without this genotype under altitude stress. The results contribute to provide scientific bases for finding these individuals in specified occupational people, ensuring their health and enhancing work efficiency.