Notch polymorphisms associated with sensitivity of noise induced hearing loss among Chinese textile factory workers.

BACKGROUND: Noise induced hearing loss (NIHL) is a polygenic disease involving both genetic and environmental factors, and is one of the most important occupational health hazards worldwide. To date, the influence of Notch1 variants on the risk to develop NIHL has not been illuminated. This study was conducted to explore the effects of Notch1 polymorphisms on individual susceptibility to NIHL. METHODS: A total of 2689 industrial workers from one textile factory in east China were recruited to participate in the current study. Venous blood was collected, basic clinical data was obtained by questionnaires and pure-tone audiometry (PTA) tests were conducted by specialist physicians. Next we performed genotyping of three selected SNPs (rs3124594, rs3124599 and rs3124603) in the Notch1 gene in 535 NIHL patients and 535 controls. Subsequently, the main effects of the genotypes and their interactions were evaluated. RESULTS: Our results revealed that individuals with a GG of rs3124594, TT of rs3124603 (OR = 4.70 and 1.59 respectively) and the haplotype AAC (rs3124594-rs3124599-rs3124603) (OR = 14.95) were associated with an increased risk of NIHL in our study cohort. Stratified analysis showed that an increased NIHL risk was found in individuals exposed to work related noise for ≤16 years that also had the rs3124594 GG or rs3124603 CT/TT genotype with an OR of 4.20 and 1.73 respectively. Multifactor dimensionality reduction analysis indicated that rs3124594, rs3124599 and rs3124603 interacted with each other and were related to an increased risk to develop NIHL (OR = 3.60). CONCLUSIONS: The genetic polymorphisms rs3124594 and rs3124603 within the Notch1 gene are associated with an increased risk of NIHL in a Chinese population and could potentially be used as biomarkers for NIHL in noise exposed workers.

Correlation between CAT polymorphism and susceptibility to DMAc-induced abnormal liver function: a case-control study of Chinese population.

CONTEXT: Acute or chronic exposure of N,N-dimethylacetamide (DMAc) is responsible for abnormal liver function. It appears that DMAc is mainly metabolized by cytochrome P450 in the liver and thereby produces reactive oxygen species (ROS). The elimination of ROS and the repairing of ROS-induced DNA damage are relevant to the ultimate toxicity of DMAc. OBJECTIVE: To investigate whether the polymorphisms in the CAT (rs564250, rs769214 and rs7943316), hOGG1 (rs2072668 and rs159153) and XRCC1 (rs25487 and rs1799782) genes are associated with susceptibility to DMAc-induced abnormal liver function in Chinese population. METHODS: Samples were obtained from 108 workers with DMAc-induced abnormal liver function and 108 workers with normal liver function. RESULTS: Subjects with the CAT rs769214 GA/GG genotypes had a reducing risk of abnormal liver function, which was more evident in the subgroups exposed to DMAc <10 years, exposed to DMAc <5 mg/m3, never smoked and never drank. CONCLUSIONS: CAT rs769214 (-844 G > A) polymorphism may be associated with DMAc-induced abnormal liver function in Chinese population.

Genetic variation in APE1 gene promoter is associated with noise-induced hearing loss in a Chinese population.

OBJECTIVE: To investigate whether the apurinic/apyrimidinic endonuclease 1 (APE1) 1349 T>G and -656 T>G polymorphisms were associated with the risk of noise-induced hearing loss (NIHL) in a Chinese population. METHODS: The two APE1 polymorphisms were analyzed among 613 NIHL workers and 613 normal hearing workers using the minor groove binder TaqMan probe assay. RESULTS: We found that the APE1 -656 TT genotype was associated with a increased risk of NIHL [adjusted odds ratio (OR) 1.46, 95% confidence interval (CI) 1.05-2.06]. This increased risk was more pronounced in the stratification analysis. Furthermore, we found that subjects with two risk genotypes (hOGG1 Cys/Cys, APE1 -656 TT) had a significantly increased risk of NIHL (adjusted OR 1.91, 95% CI 1.27-2.88). CONCLUSION: Our study identified that the APE1 -656 T>G polymorphism may contribute to the susceptibility of NIHL.

[Association between single nucleotide polymorphisms of PON2 gene and susceptibility to occupational noise-induced deafness among Chinese Han population exposed to high noise levels].

OBJECTIVE: To investigate the association between the single nucleotide polymorphisms (SNPs) of paraoxonase-2 (PON2) gene and the susceptibility to occupational noise-induced deafness among Chinese Han population exposed to high noise levels [>85 dB (A)]. METHODS: A case-control study was conducted in Chinese Han population exposed to high noise levels. The subjects were divided into case group (n = 127) and control group (n = 136) according to the Diagnostic criteria of occupational noise-induced deafness (GBZ 49-2007). The case group was composed of 127 workers with a mean binaural high-frequency hearing threshold not less than 40 dB, as measured using an electro-audiometer, while the control group was composed of 136 workers with a mean binaural high-frequency hearing threshold less than 40 dB, as measured using the electro-audiometer, who were on shift in the same position as the cases and matched with them for age, sex, and years of noise exposure. Peripheral venous blood (2 ml) was collected from each subject during physical examination to extract genomic DNA, and genotypes were identified using a TaqMan probe. RESULTS: PON2 genotypes rs7493 CG+GG, rs7785846 CT+TT, rs12026 CG+GG, and rs7786401 GT+TT were the risk factors for occupational noise-induced deafness, and the adjusted odds ratios (95%confidence intervals) were 5.87 (3.11∼11.07), 5.92 (3.10∼11.32), 5.53 (2.93∼10.45), and 5.93 (3.10∼11.34), respectively. In addition, the higher the noise exposure levels, the higher the risk of developing occupational noise-induced deafness among the individuals carrying mutant genotypes. CONCLUSION: PON2 genotypes rs7493 CG+GG, rs7785846 CT+TT, rs12026 CG+GG, and rs7786401 GT +TT may be associated with the susceptibility to occupational noise-induced deafness among Chinese Han population exposed to high noise levels, and the effects of mutant genotypes and noise exposure levels may be mutually enhanced.

Effects of long-term high-level lead exposure on the immune function of workers.

This work was undertaken to study the immunomodulatory effects of long-term exposure to varying levels of lead (Pb) in workers. A total of 49 people who underwent occupational health examinations from 2009 to 2018 were selected as study subjects. Differences between the two group populations regarding the levels of T-lymphocytes, B-lymphocytes, natural killer (NK) cells, and granulocytes, as well as the levels of TH1/TH2/TH17 cytokines, were evaluated. The results indicated that the percentages of CD3+ cells in the high-Pb group were significantly higher than those in the low-Pb counterparts (p < .05). In contrast, the percentages of CD3-CD16+CD56+ cells were significantly lower in the high-Pb workers. There were no significant differences in other immunommy cells and TH1/TH2/TH17 cytokine between the groups. CD3+ cell levels in workers positively correlated with blood Pb levels (Rs = 0.378, p = .007), while the expression of CD3-CD16+CD56+ cells was negatively correlated (Rs = -0.320, p = .025). There was no significant correlation between blood Pb concentration and the other immune endpoints evaluated here.

Survival analysis of 15,402 pneumoconiosis cases in Jiangsu Province of China from 1961 to 2019.

BACKGROUND: Pneumoconiosis has been reported as one of the major global burdens of occupational health-related diseases. The global prevalence had increased since 1990. Prevention and treatment of pneumoconiosis in the project of occupational health have been a priority of the action plan of Healthy China 2030. METHODS: A life table was used to explore the survival and fatality rate of pneumoconiosis. Using Cox proportional hazards regression model, the factors of survival time were investigated. RESULTS: A total of 15,402 cases had several species of pneumoconiosis, including silicosis, coal worker pneumoconiosis and welder pneumoconiosis that accounted for 68.49%, 19.41% and 3.84% of total pneumoconiosis, respectively. Eighty percent of cases were initially diagnosed at stage I, 15.5% at stage II, and 4.5% at stage III. The overall average survival time was determined as 14.74±9.57 years, the life expectancy reached 34.324 years in total, and the total mortality of patients suffering from pneumoconiosis was 19.89%. The average dust exposure period, average survival time and life expectancy progressively decreased with the stage upgrade, whereas the age of onset and mortality rate tended to increase. Dust exposure years, initially diagnosed at stage II or stage III, stage I upgrade to stage II, stage I upgrade to stage III and low economic level were found as important risk factors for the survival of patients suffering from pneumoconiosis. CONCLUSIONS: Stage II and stage III of pneumoconiosis may have a direct effect on the survival time of patients suffering from pneumoconiosis. The prevention and delay of the progression of pneumoconiosis are critical to prolonging the survival time of cases.

Factors Influencing Trace Element Levels in the Blood of Tin Smelting Workers.

BACKGROUND: This study is to assess the correlation between blood concentration ranges of eight elements of tin smelting workers from Guangxi Liuzhou and their job type, working years, age, and sex. METHODS: We collected blood samples of 218 tin smelting workers from a Chinese tin smelting factory and determined the levels of elements by inductively coupled plasma mass spectrometry. RESULTS: Within the blood concentrations of eight metal elements of the objects, the blood concentration of copper and zinc is affected by the job type of comprehensive work; that of arsenic and mercury is affected by refining; and that of chromium, cadmium, and lead is affected by primary smelting. CONCLUSIONS: We present the remarkable influence of four job types on the blood concentration of seven trace elements.

DNMT1 and DNMT3A haplotypes associated with noise-induced hearing loss in Chinese workers.

This study was conducted to explore the effects of DNMT1 and DNMT3A polymorphisms on susceptibility to noise-induced hearing loss (NIHL) in Chinese workers. A total of 2689 industrial workers from a single textile factory were recruited. Venous blood was collected, as were questionnaire and pure-tone audiometry (PTA) data by specialist physicians. Four selected SNPs (rs7578575, rs749131, rs1550117, and rs2228611) in DNMT1 and DNMT3A were genotyped in 527 NIHL patients and 527 controls. Then, main effects of the genotypes and their interactions were evaluated. Results revealed that the GG genotype at rs749131 and the AG/GG genotypes at rs1550117 and rs2228611 [odds ratio (OR) = 1.87, 2.57, and 1.98 respectively], as well as the haplotypes AGGG and TGGA (rs7578578-rs749131-rs1550117-rs2228611) (OR = 1.35 and 1.56, respectively) were associated with an increased risk of NIHL in the Chinese population. Multifactor dimensionality reduction analysis indicated that rs7578575, rs749131, and rs2228611 interact and are related to increased NIHL risk (OR = 1.63). The genetic polymorphisms rs749131 G, rs1550117 G, and rs2228611 G within the DNMT1 and DNMT3A genes are associated with an increased risk of NIHL in the Chinese population and have the potential to act as biomarkers for noise-exposed workers.

Association between blood lead level and blood pressure: An occupational population-based study in Jiangsu province, China.

Studies about the association between lead exposure and the elevation of blood pressure and risk of hypertension are varied, while available data on blood lead levels (BLL) in workers with lead-exposure are scarce. This research aimed to evaluate associations between BLL and blood pressure in an occupational population-based study in Jiangsu province, China. We enrolled 21,688 workers in this study. Information on socioeconomic and occupational background was obtained with face-to-face interviews. BLL, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and hypertension status was confirmed. We found that workers in mini-factories had the highest average BLL (20.3 µg/dL; 95% CI, 19.0-21.6 µg/dL) for overall participants. The employees in private factories had higher BLL (9.6 µg/dL; 95% CI, 9.5-9.8 µg/dL). However, BLL was much lower (4.0 µg/dL; 95%CI, 3.7-4.2 µg/dL) in state-owned factories. Participants working in the electrical machinery and equipment manufacturing industry had higher BLL (9.1 µg/dL; 95% CI, 9.0-9.3µg/dL). Compared to those workers with ≤ 4.6 µg/dL BLL, workers with > 17.5 µg/dL BLL presented 1.34 mmHg and 0.70 mmHg average difference in SBP and DBP, respectively. The adjusted OR for hypertension was 1.11 (95%CI, 1.08-1.15) compared to the workers with > 17.5 µg/dL BLL and to those with ≤ 4.6 µg/dL BLL. In summary, we found that BLL was positively associated with SBP and DBP and with the morbidity of hypertension in occupational populations with a high concentration of lead exposure. It is important to formulate new standards of blood lead levels to screen for elevated lead exposure. In addition, a series of new systems of risk assessment should be established to further reduce and prevent lead exposure.

Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population.

Noise induced hearing loss (NIHL), a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA) was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09 respectively) are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53). The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers.

Association of TagSNP in lncRNA HOTAIR with susceptibility to noise-induced hearing loss in a Chinese population.

BACKGROUND: Noise-induced hearing loss (NIHL) is a multifactorial disease, and dysregulation of oxidative stress is universally acknowledged as one crucial pathogenic factor for this disease. Recently studies have found the LncRNA HOTAIR is involved in the alteration of oxidative stress level, cell proliferation, cell cycle progression, and apoptosis. Considering the effects of lncRNA HOTAIR in cellular oxidative stress, we sought to investigate the influence of lncRNA HOTAIR variants on the risk of NIHL. METHODS: To explore the effects of HOTAIR polymorphisms on individual susceptibility to NIHL, We performed genotyping of three tagSNPs (rs874945, rs4759314 and rs7958904) in HOTAIR gene in a Chinese population which consists of 570 NIHL cases and 570 controls. The luciferase assays were further performed to investigate the regulatory function of HOTAIR tagSNPs. RESULTS: Our results revealed individuals with the G allele of HOTAIR tagSNP rs4759314 and the haplotype (rs874945, rs4759314 and rs7958904) are associated with an increased risk of NIHL in a Chinese population. Meanwhile, the rs4759314 G allele could significantly increase the expression of lncRNA HOTAIR. CONCLUSIONS: The genetic polymorphism within HOTAIR gene may play a crucial role in the occurrence and development of NIHL.

Genetic Variations in the Promoter of the APE1 Gene Are Associated with DMF-Induced Abnormal Liver Function: A Case-Control Study in a Chinese Population.

Acute or long-term exposure to N,N-dimethylformamide (DMF) can induce abnormal liver function. It is well known that DMF is mainly metabolized in the liver and thereby produces reactive oxygen species (ROS). The base excision repair (BER) pathway is regarded as a very important pathway involved in repairing ROS-induced DNA damage. Several studies have explored the associations between GSTM1, GSTT1, CYP2E1 polymorphisms and DMF-induced abnormal liver function; however, little is known about how common hOGG1, XRCC1 and APE1 polymorphisms and DMF induce abnormal liver function. The purpose of this study was to investigate whether the polymorphisms in the hOGG1 (rs159153 and rs2072668), XRCC1 (rs25487, rs25489, and rs1799782), APE1 (rs1130409 and 1760944) genes in the human BER pathway were associated with the susceptibility to DMF-induced abnormal liver function in a Chinese population. These polymorphisms were genotyped in 123 workers with DMF-induced abnormal liver function and 123 workers with normal liver function. We found that workers with the APE1 rs1760944 TG/GG genotypes had a reduced risk of abnormal liver function, which was more pronounced in the subgroups that were exposed to DMF for <10 years, exposed to ≥10 mg/m³ DMF, never smoked and never drank. In summary, our study supported the hypothesis that the APE1 rs1760944 T > G polymorphism may be associated with DMF-induced abnormal liver function in the Chinese Han population.

Analysis of plasma microRNA expression profiles in male textile workers with noise-induced hearing loss.

BACKGROUND: Circulating microRNAs (miRNAs) have attracted interests as non-invasive biomarkers of physiological and pathological conditions, which may be applied in noise-induced hearing loss (NIHL). However, no epidemiology studies have yet examined the potential effects of NIHL or noise exposure on miRNA expression profiles. OBJECTIVES: We sought to identify permanent NIHL-related miRNAs and to predict the biological functions of the putative genes encoding the indicated miRNAs. METHODS: In the discovery stage, we used a microarray assay to detect the miRNA expression profiles between pooled plasma samples from 10 noise-exposed individuals with normal hearing and 10 NIHL patients. In addition, we conducted a preliminary validation of six candidate miRNAs in the same 20 workers. Subsequently, three miRNAs were selected for expanded validation in 23 non-exposed individuals with normal hearing and 46 noise-exposed textile workers which including 23 noise-exposed workers with normal hearing and 23 NIHL patients. Moreover, we predicted the biological functions of the putative target genes using a Gene Ontology (GO) function enrichment analysis. RESULTS: In the discovery stage, compared with the noise exposures with normal hearing, 73 miRNAs demonstrated at least a 1.5-fold differential expression in the NIHL patients. In the preliminary validation, compared with the noise exposures, the plasma levels of miR-16-5p, miR-24-3p, miR-185-5p and miR-451a were all upregulated (P < 0.001) in the NIHL patients. In the expanded validation stage, compared with the non-exposures, the plasma levels of miR-24, miR-185-5p and miR-451a were all significantly downregulated (P < 0.001) in the exposures. And compared with the noise exposures, the plasma levels of miR-185-5p and miR-451a were slightly elevated (P < 0.001) in the NIHL patients, which were consistent with the results of preliminary validation and microarray analysis. CONCLUSION: The two indicated plasma miRNAs may be biomarkers of indicating responses to noise exposure. However, further studies are necessary to prove the causal association between miRNAs changes and noise exposure, and to determine whether these two miRNAs are clear biomarkers to noise exposure.

A functional Ser326Cys polymorphism in hOGG1 is associated with noise-induced hearing loss in a Chinese population.

DNA damage to cochlear hair cells caused by 8-oxoguanine (8-oxoG) is essential for the development of noise-induced hearing loss (NIHL). Human 8-oxoG DNA glycosylase1 (hOGG1) is a key enzyme in the base excision repair (BER) pathway that eliminates 8-oxoG. Many epidemiological and functional studies have suggested that the hOGG1 Ser326Cys polymorphism (rs1052133) is associated with many diseases. The purpose of this investigation was to investigate whether the hOGG1 Ser326Cys polymorphism in the human BER pathway is associated with genetic susceptibility to NIHL in a Chinese population. This polymorphism was genotyped among 612 workers with NIHL and 615 workers with normal hearing. We found that individuals with the hOGG1 Cys/Cys genotype had a statistically significantly increased risk of NIHL compared with those who carried the hOGG1 Ser/Ser genotype (adjusted OR=1.59, 95% CI=1.13-2.25) and this increased risk was more pronounced among the workers in the 15- to 25- and >25-year noise exposure time, 85-92 dB(A) noise exposure level, ever smoking, and ever drinking groups, similar effects were also observed in a recessive model. In summary, our data suggested that the hOGG1 Cys/Cys genotype may be a genetic susceptibility marker for NIHL in the Chinese Han population.

Association between paraoxonase 2 gene polymorphisms and noise-induced hearing loss in the Chinese population.

OBJECTIVES: The aim of the present study was to investigate whether PON2 gene polymorphisms (rs7493, rs12026, rs12704796, rs7785846 and rs7786401) are associated with susceptibility to noise-induced hearing loss (NIHL) in the Chinese population. METHODS: A case-control study was conducted using 615 cases selected without any restriction in age or sex and 644 controls who were matched with the cases in terms of age, gender and the intensity and duration of exposure to noise. Information on these subjects was gathered by questionnaires that were administered through face-to-face interviews by trained interviewers. RESULTS: We found that the rs7493 CG + GG genotype (OR=1.36, 95% CI, 1.08-1.72), rs12026 CG + GG genotype (OR=1.34, 95% CI, 1.06-1.70), rs7785846 CT + TT genotype (OR=1.36, 95% CI, 1.07-1.71) and rs7786401 GT + TT genotype (OR=1.33, 95% CI, 1.05-1.68) were risk factors for NIHL. CONCLUSIONS: PON2 gene polymorphisms may be associated with susceptibility to NIHL in the Chinese population

Genetic variation in GSTM1 is associated with susceptibility to noise-induced hearing loss in a Chinese population.

OBJECTIVES: To investigate whether glutathione S-transferases (GST) genetic polymorphisms (GSTT1 rs1049055, GSTM1 rs10712361, and GSTP1 rs1695) are associated with susceptibility to noise-induced hearing loss (NIHL). METHODS: These polymorphisms were analyzed in 444 NIHL and 445 normal hearing workers. In addition, total plasma GST activity was measured in all subjects. RESULTS: Individuals with the GSTM1 null genotype had a statistically significantly increased risk of NIHL (odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.26 to 2.13) compared with those carrying a wild-type GSTM1 genotype. This effect was more pronounced among the workers exposed to 86 to 91 dB(A) (OR = 3.35, 95% CI = 1.54 to 7.31). Glutathione S-transferase activity of the NIHL workers was also lower than that of normal hearing workers (14.5 ± 5.1 U/ml vs 15.9 ± 6.3 U/ml, P = 0.010). CONCLUSION: Our results suggest that GSTM1 polymorphism is associated with susceptibility to NIHL.