Lifestyle factors modified the mediation role of liver fibrosis in the association between occupational physical activity and blood pressure.

Objectives: The study aimed to estimate the role of liver fibrosis in the association between occupational physical activity (OPA) and blood pressure (BP), which is modified by lifestyle factors. Methods: The questionnaire survey and physical examination were completed among 992 construction workers in Wuhan, China. Associations between OPA or lifestyle factors and liver fibrosis indices and blood pressure were assessed using generalized additive models. The mediation analysis was used to evaluate the role of liver fibrosis in the association between OPA and lifestyle factors and BP. Results: Moderate/high OPA group workers had an increased risk of liver fibrosis [odds ratio (OR) = 1.69, 95% confidence intervals (CI): 1.16-2.47, P < 0.05] compared with low OPA group workers. Smoking or drinking alcohol was related to liver fibrosis (aspartate aminotransferase to platelet ratio index: OR = 2.22, 95% CI: 1.07-4.62 or OR = 2.04, 95% CI: 1.00-4.15; P < 0.05). Compared with non-drinkers, drinkers were related to a 2.35-mmHg increase in systolic blood pressure (95% CI: 0.09-4.61), and a 1.60-mmHg increase in diastolic blood pressure (95% CI: 0.08-3.13; P < 0.05). We found a significant pathway, "OPA → liver fibrosis → blood pressure elevation," and lifestyle factors played a regulatory role in the pathway. Conclusion: OPA or lifestyle factors were associated with liver fibrosis indices or BP in construction workers. Furthermore, the association between OPA and BP may be partially mediated by liver fibrosis; lifestyle factors strengthen the relationship between OPA and BP and the mediation role of liver fibrosis in the relationship.

Occupational noise and genetic variants in stress hormone biosynthesis-based genes and rates of blood lipid changes in China: A five-year longitudinal study.

Lipid profiles are influenced by both noise and genetic variants. However, little is known about the associations of occupational noise and genetic variants with age-related changes in blood lipids, a crucial event in the initiation and evolution of atherosclerotic cardiovascular diseases. We aimed to evaluate the associations of blood lipid change rates with occupational noise and genetic variants in stress hormone biosynthesis-based genes. This cohort was established in 2012 and 2013 and was followed up until 2017. A total of 952 participants were included in the final analysis and all of them were categorized to two groups, the exposed group and control group, according to the exposed noise levels in their working area. Single nucleotide polymorphisms (SNPs) in stress hormone biosynthesis-based genes were genotyped. Five physical examinations were conducted from 2012 to 2017 and lipid measurements were repeated five times. The estimated annual changes (EACs) of blood lipid were calculated as the difference in blood lipid levels between any 2 adjacent examinations divided by their time interval (year). The generalized estimating equations for repeated measures analyses with exchangeable correlation structures were used to evaluate the influence of exposing to noise (versus being a control) and the SNPs mentioned above on the EACs of blood lipids. We found that the participants experienced accelerated age-related decline in high-density lipoprotein cholesterol (HDL-C) levels as they were exposed to noise (ß = -0.38, 95% confidence interval (CI), -0.66 to -0.10, P = 0.007), after adjusting for work duration, gender, smoking, alcohol consumption, and pack-years. This trend was only found in participants with COMT-rs165815 TT genotype (ß = -1.19, 95% CI, -1.80 to -0.58, P < 0.001), but not in those with the CC or CT genotypes. The interaction of noise exposure and rs165815 was marginally significant (Pinteraction = 0.010) after multiple adjustments. Compared with DDC-rs11978267 AA genotype carriers, participants carrying rs11978267 GG genotype had decreased EAC of triglycerides (TG) (ß = -5.06, 95% CI, -9.07 to -1.05, P = 0.013). Participants carrying DBH-rs4740203 CC genotype had increased EAC of total cholesterol (TC) (ß = 1.19, 95% CI, 0.06 to 2.33, P = 0.039). However, these findings were not statistically significant after multiple adjustments. These results indicated that Occupational noise exposure was associated with accelerated age-related decreases in HDL-C levels, and the COMT-rs165815 genotype appeared to modify the effect of noise exposure on HDL-C changes among the occupational population.

Risk for lung-related diseases associated with welding fumes in an occupational population: Evidence from a Cox model.

Background: Welding fumes are a risk factor for welder pneumoconiosis. However, there is a lack of population information on the occurrence of welding fume-induced lung cancer, and little is known about the welding fume pathogenesis. Methods: Welding fume and metal ion concentrations were assessed in a vehicle factory in Wuhan. A Cox regression model estimated lung-related disease risk in workers by independent and combined factors. Results: Workers' exposures were divided into four grades; the highest exposure was among the welders in the maintenance workshop, the highest Mn and Fe exposure was 4 grades, and the highest Cr exposure was 3 grades. Subgroup analysis found that the risk of lung-related disease was 2.17 (95% CI: 1.31-3.57, p < 0.05) in welders compared with non-welders, and the risk of pulmonary disease in male welders was 2.24 (95% CI: 1.34-3.73, p < 0.05) compared to non-welders. Smoking welders had a 2.44 (95% CI: 1.32-4.51, p < 0.01) higher incidence of lung-related diseases than non-welders. Total years of work as an independent protective factor for lung-related disease risk was 0.72 (95% CI: 0.66-0.78, p < 0.01). As an independent risk factor, high-high and high-low exposure had a 5.39 (95% CI: 2.52-11.52, p < 0.001) and 2.17 (95% CI: 1.07-4.41, p < 0.05) higher risk for lung-related diseases, respectively. Conclusions: High welding fume exposure is a significant risk factor for lung-related disease in workers.

Stress hormone biosynthesis-based genes and lifestyle moderated the association of noise exposure with blood pressure in a cohort of Chinese tobacco factory workers: A cross-sectional analysis.

When evaluating noise-related cardiovascular risk, noise is generally solely assessed as the major stressor. However, cardiovascular effect of other simultaneous exposure events, such as unhealthy lifestyle and genetic variation, is easily neglected. The aim of this study is to estimate the combined effect of noise and lifestyle on blood pressure alteration, particularly under different genetic background. This study included 536 workers from a tobacco factory in Wuhan, China, who were divided into high exposure group and low exposure group according to noise measurement in their working area. All participants took annual physical examination and questionnaire survey to provide information on individual systolic and diastolic blood pressure (SBP and DBP) and lifestyle (smoking, drinking and physical activity). Single nucleotide polymorphism at genes related to stress hormone production were determined. Moderated moderation models were constructed to investigate the interaction effect of noise exposure and lifestyle factors on blood pressure with regard to different genetic background. We identified an expected trend in association between noise exposure and SBP among active smokers (P = 0.086). The moderated moderation analysis showed significant three-way interaction effect (COMT rs4680 × smoking status × noise exposure levels) on SBP or DBP (both P < 0.05). For COMT rs4680 GA+AA genotype carriers, active smoking significantly moderated the association between noise exposure and SBP or DBP (both P < 0.05). The results indicated that for COMT rs4680 A allele carriers, tobacco and noise exposure contribute collectively to blood pressure alteration, supporting that stress hormone production may play a certain role in the smoke-and-noise-induced cardiovascular effect.

Association of occupational noise exposure, bilateral hearing loss with atherosclerotic cardiovascular disease risk in Chinese adults.

We aimed to explore the association of occupational noise exposure with atherosclerotic cardiovascular disease (ASCVD) risk in Chinese adults. We included 21,412 participants from the Dongfeng-tongji Cohort Study, occupational noise exposure was evaluated through workplace noise level and/or the job titles, hearing loss was defined as a pure-tone mean of 25 dB or higher at 0.5, 1, 2, and 4 kHz in any ear. Compared with participants without occupational noise exposure, the 10-year ASCVD risk was significantly higher for noise exposure duration ≥20 years (OR = 1.20, 95%CI = 1.05-1.32) after adjusting for potential confounders. In the subgroup analysis, the association was only statistically significant in males (OR = 1.86, 95%CI = 1.12-3.14) and participants aged equal to or over 60 years old (OR = 1.20, 95%CI = 1.05-1.33), but not in females (OR = 1.15, 95%CI = 0.71-1.92) and aged below 60 (OR = 1.51, 95%CI = 0.75-2.85). In the subsample analyses (N = 10,165), bilateral hearing loss was associated with a higher risk of 10-year ASCVD (OR = 1.72, 95%CI = 1.30-2.30), especially for participants who were males (OR = 2.40, 95%CI = 1.61-3.42) and aged equal to or over 60 (OR = 1.85, 95%CI = 1.40-2.44). The present study suggests that occupational noise exposure may be a potential risk factor for ASCVD, especially for males and older participants.

Is job strain associated with a higher risk of type 2 diabetes mellitus? A systematic review and meta-analysis of prospective cohort studies.

OBJECTIVES: Epidemiological studies have explored the relationship between work-related stress and the risk of type 2 diabetes mellitus (T2DM), but it remains unclear on whether work-related stress could increase the risk of T2DM. We aimed to evaluate the association between job strain and the risk of T2DM. METHODS: We searched PubMed and Web of Science up to April 2019. Summary risk estimates were calculated by random-effect models. And the analysis was also conducted stratifying by gender, study location, smoking, drinking, body mass index, physical activity, family history of T2DM, education and T2DM ascertainment. Studies with binary job strain and quadrants based on the job strain model were analyzed separately. RESULTS: A total of nine studies with 210 939 participants free of T2DM were included in this analysis. High job strain (high job demands and low control) was associated with the overall risk of T2DM compared with no job strain (all other combinations) [relative risk (RR) 1.16, 95% confidence interval (CI) 1.03-1.31], and the association was more evident in women (RR 1.48, 95% CI 1.02-2.14). A statistically significant association was also observed when using high strain as a category (job strain quadrants) rather than binary variable (RR 1.62, 95% CI 1.04-2.55) in women but not men. CONCLUSIONS: Our study suggests that job strain is an important risk factor for T2DM, especially among women. Appropriate preventive interventions in populations with high job strain would contribute to a reduction in T2DM risk.

Association of urinary metal profiles with serum uric acid: a cross-sectional study of traffic policemen in Wuhan, China.

OBJECTIVES: Serum uric acid (SUA) is both a strong antioxidant and one of the key risk factors of cardiovascular diseases (CVDs). We aimed to investigate the associations of urinary metal profile with SUA in traffic policemen in Wuhan, China. DESIGN: A cross-sectional study was carried out in traffic policemen. SETTING: A seriously polluted Chinese city. PARTICIPANTS: A total of 186 traffic policemen were recruited in this study. About 56 of them worked in the logistics department and the other 130 maintained traffic order or dealt with traffic accidents on the roads. All these subjects had worked as a policeman for at least 1 year. MAIN OUTCOME MEASURES: SUA. RESULTS: The significantly negative association of lead with SUA was consistent between single-metal and multiple-metal models (p=0.004 and p=0.020, respectively). Vanadium, chromium and tin were reversely associated with SUA levels in the single-metal models after false discovery rate (FDR) adjustment (all P_FDR < 0.05). One IQR increase in vanadium, chromium, tin and lead was associated with 26.9 µmol/L (95% CI -44.6 to -9.2; p=0.003), 27.4 µmol/L (95% CI -46.1 to -8.8; p=0.004), 11.2 µmol/L (95% CI -18.9 to -3.4; p=0.005) and 16.4 µmol/L (95% CI -27.6 to -5.2; p=0.004) decrease in SUA, respectively. Significant interaction between smoking and vanadium on decreased SUV was found (pfor interaction = 0.007 and p_FDR = 0.028). CONCLUSIONS: Urinary vanadium, chromium, tin and lead were negatively associated with SUA. Vanadium and cigarette smoking jointly affected SUA levels. Further studies are needed to replicate these findings and to investigate the potential mechanisms.

Co-exposure to metals and polycyclic aromatic hydrocarbons, microRNA expression, and early health damage in coke oven workers.

BACKGROUND: All humans are now co-exposed to multiple toxic chemicals, among which metals and polycyclic aromatic hydrocarbons (PAHs) are of special concern as they are often present at high levels in various human environments. They can also induce similar early health damage, such as genetic damage, oxidative stress, and heart rate variability (HRV). Exposure to metals, PAHs, and their combined pollutants can alter microRNA (miRNA) expression patterns. OBJECTIVES: To explore the associations of metal-PAH co-exposure with miRNA expression, and of the associated miRNAs with early health damage. METHODS: We enrolled 360 healthy male coke oven workers and quantified their exposure levels of metals and PAHs by urinary metals, urinary monohydroxy-PAHs (OH-PAHs), and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, respectively. We selected and measured ten miRNAs: let-7b-5p, miR-126-3p, miR-142-5p, miR-150-5p, miR-16-5p, miR-24-3p, miR-27a-3p, miR-28-5p, miR-320b, and miR-451a. For miRNAs influenced by the effect modification of metals or PAHs and/or metal-PAH interactions, we further evaluated their associations with biomarkers for genetic damage, oxidative stress, and HRV. RESULTS: After adjusting for PAHs and other metals, miRNA expression was found to be negatively associated with aluminum, antimony, lead, and titanium, and positively associated with molybdenum and tin (p < 0.05). Antimony showed modifying effects on the PAH-miRNA associations, while OH-PAHs and BPDE-Alb adducts modified the associations of metals with miRNAs (p for modifying effect < 0.05). Furthermore, miRNA expression was influenced by the antagonistic interactions between antimony and OH-PAHs, and by the synergistical interactions between metals and BPDE-Alb adducts (pinteraction < 0.05). Let-7b-5p, miR-126-3p, miR-16-5p, and miR-320b were additionally found to be associated with increased genetic damage in the present study [false discovery rate (FDR)-adjusted p < 0.05]. CONCLUSIONS: Associations of metal-PAH co-exposure with miRNA expression, and of associated miRNAs with early health damage, suggested potential mechanistic connections between the complex metal-PAH interactions and their deleterious effects that are worthy of further investigation.

Exposure to Polycyclic Aromatic Hydrocarbons, Plasma Cytokines, and Heart Rate Variability.

Epidemiological studies have suggested associations between polycyclic aromatic hydrocarbons (PAHs) and heart rate variability (HRV). However, the roles of plasma cytokines in these associations are limited. In discovery stage of this study, we used Human Cytokine Antibody Arrays to examine differences in the concentrations of 280 plasma cytokines between 8 coke-oven workers and 16 community residents. We identified 19 cytokines with significant different expression (fold change ≥2 or ≤-2, and q-value <5%) between exposed workers and controls. 4 cytokines were selected to validate in 489 coke-oven workers by enzyme-linked immunosorbent assays in validation stage. We found OH-PAHs were inversely associated with brain-derived neurotrophic factor (BDNF) (p < 0.05), and interquartile range (IQR) increases in OH-PAHs were associated with >16% BDNF decreases. Additionally, OH-PAHs were positively associated with activated leukocyte cell adhesion molecule (ALCAM) and C-reactive protein (CRP) (p < 0.05), and IQR increases in OH-PAHs were associated with >20% increases in CRP. We also found significant associations between these cytokines and HRV (p < 0.05), and IQR increases in BDNF and CRP were associated with >8% decreases in HRV. Our results indicated PAH exposure was associated with plasma cytokines, and higher cytokines were associated with decreased HRV, but additional human and potential mechanistic studies are needed.

Polycyclic Aromatic Hydrocarbons-Associated MicroRNAs and Heart Rate Variability in Coke Oven Workers.

OBJECTIVE: We aimed to evaluate the association between polycyclic aromatic hydrocarbons (PAHs)-related microRNAs (miRNAs) and heart rate variability indices in coke oven workers. METHODS: We recruited 365 male coke oven workers and measured urinary PAH metabolites by gas chromatography-mass spectrometry. Five heart rate variability indices were measured using three-channel Holter monitor. Six miRNAs were detected by TaqMan miRNA assays (Life Technologies, Foster City, CA). RESULTS: miR-24-3p, miR-27a-3p, miR-142-5p, and miR-320b were negatively associated with the root mean of square of successive differences between adjacent normal NN intervals (RMSSD) (P(trend) = 0.006, 0.047, 0.019, 0.011, respectively). miR-142-5p and miR-320b were also negatively associated with standard deviation of all normal to normal NN intervals (SDNN) (P(trend) = 0.01 and 0.035). miR-24-3p, miR-27a-3p, and miR-320b were significantly interacted with multiple PAH metabolites and influenced heart rate variability indices, whereas miR-24-3p also significantly interacted with smoking to influence low frequency (P(interaction) < 0.05 for all). CONCLUSIONS: Plasma miRNAs might act as potential biomarkers for the adverse effect of PAH exposure on the cardiovascular system.

A solute carrier family 22 member 3 variant rs3088442 G→A associated with coronary heart disease inhibits lipopolysaccharide-induced inflammatory response.

Recent genome-wide association studies have identified single-nucleotide polymorphism (SNPs) within the SLC22A3 (solute carrier family 22 member 3) gene associated with coronary heart disease (CHD) in the Caucasian population. We performed molecular analysis to investigate the potential role of SLC22A3 variants in CHD. Our study showed that the common polymorphism rs3088442 G→A, which is localized in the 3' UTR of the SLC22A3 gene, was associated with a decreased risk of CHD in the Chinese population by a case control study. In silico analysis indicated that G→A substitution of SNP rs3088442 created a putative binding site for miR-147 in the SLC22A3 mRNA. By overexpressing miR-147 or inhibiting endogenous miR-147, we demonstrated that SNP rs3088442 G→A recruited miR-147 to inhibit SLC22A3 expression. Moreover, SLC22A3 deficiency significantly decreased LPS-induced monocytic inflammatory response by interrupting NF-κB and MAPK signaling cascades in a histamine-dependent manner. Notably, the expression of SLC22A3(A) was also suppressed by LPS stimulus. Our findings might indicate a negative feedback mechanism against inflammatory response by which SLC22A3 polymorphisms decreased the risk of CHD.

Associations of the uric acid related genetic variants in SLC2A9 and ABCG2 loci with coronary heart disease risk.

BACKGROUND: Multiple studies investigated the associations between serum uric acid and coronary heart disease (CHD) risk. However, further investigations still remain to be carried out to determine whether there exists a causal relationship between them. We aim to explore the associations between genetic variants in uric acid related loci of SLC2A9 and ABCG2 and CHD risk in a Chinese population. RESULTS: A case-control study including 1,146 CHD cases and 1,146 controls was conducted. Association analysis between two uric acid related variants (SNP rs11722228 in SLC2A9 and rs4148152 in ABCG2) and CHD risk was performed by logistic regression model. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Compared with subjects with A allele of rs4148152, those with G allele had a decreased CHD risk and the association remained significant in a multivariate model. However, it altered to null when BMI was added into the model. No significant association was observed between rs11722228 and CHD risk. The distribution of CHD risk factors was not significantly different among different genotypes of both SNPs. Among subjects who did not consume alcohol, the G allele of rs4148152 showed a moderate protective effect. However, no significant interactions were observed between SNP by CHD risk factors on CHD risk. CONCLUSIONS: There might be no association between the two uric acid related SNPs with CHD risk. Further studies were warranted to validate these results.

Urinary metals and heart rate variability: a cross-sectional study of urban adults in Wuhan, China.

BACKGROUND: Epidemiological studies have suggested an association between external estimates of exposure to metals in air particles and altered heart rate variability (HRV). However, studies on the association between internal assessments of metals exposure and HRV are limited. OBJECTIVES: The purpose of this study was to examine the potential association between urinary metals and HRV among residents of an urban community in Wuhan, China. METHODS: We performed a cross-sectional analysis of 23 urinary metals and 5-min HRV indices (SDNN, standard deviation of normal-to-normal intervals; r-MSSD, root mean square of successive differences in adjacent normal-to-normal intervals; LF, low frequency; HF, high frequency; TP, total power) using baseline data on 2,004 adult residents of Wuhan. RESULTS: After adjusting for other metals, creatinine, and other covariates, natural log-transformed urine titanium concentration was positively associated with all HRV indices (all p < 0.05). Moreover, we estimated negative associations between cadmium and r-MSSD, LF, HF, and TP; between lead and r-MSSD, HF, and TP; and between iron, copper, and arsenic and HF, SDNN, and LF, respectively, based on models adjusted for other metals, creatinine, and covariates (all p < 0.10). Several associations differed according to cardiovascular disease risk factors. For example, negative associations between cadmium and r-MSSD were stronger among participants ≤ 52 years of age (vs. > 52), current smokers (vs. nonsmokers), body mass index < 25 kg/m2 (vs. ≥ 25), and among those who were not hypertensive. CONCLUSIONS: Urine concentrations of several metals were associated with HRV parameters in our cross-sectional study population. These findings need replication in other studies with adequate sample sizes.

A multilocus genetic risk score predicts coronary heart disease risk in a Chinese Han population.

OBJECTIVE: Genome-wide association studies have identified multiple genetic loci associated with coronary heart disease (CHD) risk. However, whether these loci could improve the CHD risk prediction is unclear. METHODS AND RESULTS: The present case-control study (1146 CHD cases and 1146 controls) genotyped 19 recently discovered SNPs that associated with CHD risk. As a result, 10 SNPs were successfully replicated with odds ratios (ORs) ranging from 1.16 to 1.78 (P = 4.6 × 10(-2) to 5.99 × 10(-6)). A genetic risk score was constructed to assess the combined effects of the susceptibility loci on CHD risk. Subject in the second tertile (OR = 1.32, 95% CI, 1.02-1.73, P = 3.84 × 10(-2)) and the third tertile (OR = 2.62, 95% CI, 2.00-3.43, P = 3.18 × 10(-12)) had an increased risk of CHD comparing with those in the first genetic risk score tertile after adjustment for traditional risk factors including family history of CHD. Addition of the genetic risk score to the traditional model significantly improved the net reclassification as measured by the net reclassification index (NRI) (4.82%, P = 0.0001), however, no significant improvement was observed in discrimination of CHD, the area under the receiver operating characteristic curve (AUC) increased from 0.811 to 0.822 (P = 0.18). CONCLUSIONS: A multilocus genetic risk score was associated with CHD risk in a Chinese Han population. This genetic risk score improved the net reclassification but not improved the CHD discrimination. The potential clinical use of this variations remains to be defined.

Associations between 25 lung cancer risk-related SNPs and polycyclic aromatic hydrocarbon-induced genetic damage in coke oven workers.

BACKGROUND: Genome-wide association studies (GWAS) have identified multiple single-nucleotide polymorphisms (SNP) associated with lung cancer. However, whether these SNPs are associated with genetic damage, a crucial event in cancer initiation and evolution, is still unknown. We aimed to establish associations between these SNPs and genetic damage caused by the ubiquitous carcinogens, polycyclic aromatic hydrocarbons (PAH). METHODS: We cross-sectionally investigated the associations between SNPs from published GWAS for lung cancer in Asians and PAH-induced genetic damage in 1,557 coke oven workers in China. Urinary PAH metabolites, plasma benzo[a]pyrene-r-7,t-8,c-10-tetrahydrotetrol-albumin (BPDE-Alb) adducts, urinary 8-hydroxydeoxyguanosine (8-OHdG), and micronuclei (MN) frequency were determined by gas chromatography-mass spectrometry, sandwich ELISA, high-performance liquid chromatography, and cytokinesis-block micronucleus assay, respectively. RESULTS: 13q12.12-rs753955C was suggestively associated with elevated 8-OHdG levels (P = 0.003). Higher 8-OHdG levels were observed in individuals with rare allele homozygotes (CC) than in TT homozygotes (ß, 0.297; 95% confidence interval, 0.124-0.471; P = 0.001). 9p21-rs1333040C, 10p14-rs1663689G, and 15q25.1-rs3813572G were significantly associated with lower MN frequency (P values were 0.002, 0.001, and 0.005, respectively). 10p14-rs1663689G polymorphism downregulated the relationship of the total concentration of PAH metabolites to 8-OHdG levels (Pinteraction = 0.002). TERT-rs2736100G and VTI1A-rs7086803A aggravated the relationship of BPDE-Alb adducts to MN frequency, whereas BPTF-rs7216064G attenuated that correlation (all Pinteraction < 0.001). CONCLUSIONS: Lung cancer risk-associated SNPs and their correlations with PAH exposure were associated with 8-OHdG levels and MN frequency. IMPACT: Lung cancer risk-associated SNPs might influence one's susceptibility to genetic damage caused by PAHs. Cancer Epidemiol Biomarkers Prev; 23(6); 986-96. ©2014 AACR.

Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons.

BACKGROUND: Ubiquitous polycyclic aromatic hydrocarbons (PAHs) have been shown to alter gene expression patterns and elevate micronuclei (MN) frequency, but the underlying mechanisms are largely unknown. MicroRNAs (miRNAs) are key gene regulators that may be influenced by PAH exposures and mediate their effects on MN frequency. OBJECTIVES: We sought to identify PAH-associated miRNAs and evaluate their associations with MN frequency. METHODS: We performed a two-stage study in healthy male coke oven workers to identify miRNAs associated with PAH exposures quantified using urinary monohydroxy-PAHs and plasma benzo[a]pyrene-r-7,t-8,c-10-tetrahydrotetrol-albumin (BPDE-Alb) adducts. In the discovery stage, we used Solexa sequencing to test differences in miRNA expression profiles between pooled plasma samples from 20 exposed workers and 20 controls. We then validated associations with eight selected miRNAs in 365 workers. We further evaluated associations between the PAH-associated miRNAs and MN frequency. RESULTS: In the discovery stage, miRNA expression profiles differed between the exposed and control groups, with 68 miRNAs significantly down-regulated [fold change (FC) ≤ -5] and 3 miRNAs mildly up-regulated (+2 ≤ FC < +5) in the exposed group. In the validation analysis, urinary 4-hydroxyphenanthrene and/or plasma BPDE-Alb adducts were associated with lower miR-24-3p, miR-27a-3p, miR-142-5p, and miR-28-5p expression (p < 0.030). Urinary 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyphenanthrene, and the sum of monohydroxy-PAHs were associated with higher miR-150-5p expression (p < 0.030). These miRNAs were associated with higher MN frequency (p < 0.005), with stronger associations in drinkers (pinteraction < 0.015). CONCLUSIONS: Associations of PAH exposures with miRNA expression, and of miRNA expression with MN frequency, suggest potential mechanisms of adverse effects of PAHs that are worthy of further investigation.

Circulating MicroRNAs and the occurrence of acute myocardial infarction in Chinese populations.

BACKGROUND: Circulating microRNAs ( miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. METHODS AND RESULTS: In the discovery stage, the plasma of 20 patients with AMI and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 patients with AMI and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays and further replicated in 150 patients with AMI and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in patients with AMI than in controls in both validation populations (P<0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio, 4.71; 95% confidence interval, 2.96-7.48 and odds ratio, 4.27; 95% confidence interval, 2.84-6.41, respectively). Addition of the 2 miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% confidence interval, 0.787-0.856) to 0.871 (95% confidence interval, 0.842-0.900), with a net reclassification improvement of 20.45% (P<0.0001) and an integrated discrimination improvement of 0.16 (P<0.0001) for patients with AMI. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for coronary heart disease in human vascular endothelial cells. CONCLUSIONS: The plasma levels of miR-320b and miR-125b were significantly lower in patients with AMI when compared with controls, and these miRNAs may be involved in the pathogenesis of coronary heart disease.

A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population.

BACKGROUND: Uric acid (UA) is a complex phenotype influenced by both genetic and environmental factors as well as their interactions. Current genome-wide association studies (GWASs) have identified a variety of genetic determinants of UA in Europeans; however, such studies in Asians, especially in Chinese populations remain limited. METHODS: A two-stage GWAS was performed to identify single nucleotide polymorphisms (SNPs) that were associated with serum uric acid (UA) in a Chinese population of 12,281 participants (GWAS discovery stage included 1452 participants from the Dongfeng-Tongji cohort (DFTJ-cohort) and 1999 participants from the Fangchenggang Area Male Health and Examination Survey (FAMHES). The validation stage included another independent 8830 individuals from the DFTJ-cohort). Affymetrix Genome-Wide Human SNP Array 6.0 chips and Illumina Omni-Express platform were used for genotyping for DFTJ-cohort and FAMHES, respectively. Gene-environment interactions on serum UA levels were further explored in 10,282 participants from the DFTJ-cohort. RESULTS: Briefly, we identified two previously reported UA loci of SLC2A9 (rs11722228, combined P = 8.98 × 10-31) and ABCG2 (rs2231142, combined P = 3.34 × 10-42). The two independent SNPs rs11722228 and rs2231142 explained 1.03% and 1.09% of the total variation of UA levels, respectively. Heterogeneity was observed across different populations. More importantly, both independent SNPs rs11722228 and rs2231142 were nominally significantly interacted with gender on serum UA levels (P for interaction = 4.0 × 10-2 and 2.0 × 10-2, respectively). The minor allele (T) for rs11722228 in SLC2A9 has greater influence in elevating serum UA levels in females compared to males and the minor allele (T) of rs2231142 in ABCG2 had stronger effects on serum UA levels in males than that in females. CONCLUSIONS: Two genetic loci (SLC2A9 and ABCG2) were confirmed to be associated with serum UA concentration. These findings strongly support the evidence that SLC2A9 and ABCG2 function in UA metabolism across human populations. Furthermore, we observed these associations are modified by gender.