Contribution of Genetic Polymorphisms in Human Health.

Human health is influenced by various factors; these include genetic inheritance, behavioral lifestyle, socioeconomic and environmental conditions, and public access to care and therapies in case of illness, with the support of the national health system. All these factors represent the starting point for the prevention and promotion of a healthy lifestyle. However, it is not yet clear to what extent these factors may actually affect the health of an entire population. The exposures to environmental and occupational factors are several, most of which might be poorly known, contributing to influencing individual health. Personal habits, including diet, smoking, alcohol, and drug consumption, together with unhealthy behaviors, may inevitably lead people to the development of chronic diseases, contributing to increasing aging and decreasing life expectancy. In this article, we highlight the role of susceptibility biomarkers, i.e., the genetic polymorphisms of individuals of different ethnicities, with particular attention to the risk factors in the response to specific exposures of Europeans. Moreover, we discuss the role of precision medicine which is representing a new way of treating and preventing diseases, taking into account the genetic variability of the individual with each own clinical history and lifestyle.

MicroRNA expression is associated with auditory dysfunction in workers exposed to ototoxic solvents and noise.

This study is part of a project on early hearing dysfunction induced by combined exposure to volatile organic compounds (VOCs) and noise in occupational settings. In a previous study, 56 microRNAs were found differentially expressed in exposed workers compared to controls. Here, we analyze the statistical association of microRNA expression with audiometric hearing level (HL) and distortion product otoacoustic emission (DPOAE) level in that subset of differentially expressed microRNAs. The highest negative correlations were found; for HL, with miR-195-5p and miR-122-5p, and, for DPOAEs, with miR-92b-5p and miR-206. The homozygous (mut) and heterozygous (het) variants of the gene hOGG1 were found disadvantaged with respect to the wild-type (wt), as regards the risk of hearing impairment due to exposure to VOCs. An unsupervised artificial neural network (auto contractive map) was also used to detect and show, using graph analysis, the hidden connections between the explored variables. These findings may contribute to the formulation of mechanistic hypotheses about hearing damage due to co-exposure to noise and ototoxic solvents.

Direct and Oxidative DNA Damage in a Group of Painters Exposed to VOCs: Dose - Response Relationship.

Volatile organic compounds (VOCs) are present in several working activities. This work is aimed at comparing oxidative stress and DNA damage biomarkers to specific VOCs in the occupational exposure of painters. Dose-response relationships between biomarkers of oxidative stress and of dose were studied. Unmetabolized VOCs and their urinary metabolites were analyzed. Urinary Methylhyppuric acids (MHIPPs, xylenes metabolite), Phenylglyoxylic and Mandelic acid (PGA, MA ethylbenzene metabolites), S-Benzylmercapturic acid (SBMA, toluene metabolite), and S-Phenylmercapturic acid (SPMA, benzene metabolite) were quantified at the end of work-shift. Oxidative stress was determined by: urinary excretion of 8-oxodGuo, 8-oxoGua and 8-oxoGuo and direct/oxidative DNA damage in blood by Fpg-Comet assay. Multivariate linear regression models were used to assess statistical significance of the association between dose and effect biomarkers. The regressions were studied with and without the effect of hOGG1 and XRCC1 gene polymorphisms. Statistically significant associations were found between MHIPPs and both 8-oxoGuo and oxidative DNA damage effect biomarkers measured with the Comet assay. Oxidative DNA damage results significantly associated with airborne xylenes and toluene, whilst 8-oxodGuo was significantly related to urinary xylenes and toluene. Direct DNA damage was significantly associated to SBMA. XRCC1 wild-type gene polymorphism was significantly associated with lower oxidative and total DNA damage with respect to heterozygous and mutant genotypes. The interpretation of the results requires some caution, as the different VOCs are all simultaneously present in the mixture and correlated among them.

Occupational exposure to volatile organic compounds affects microRNA profiling: Towards the identification of novel biomarkers.

In the framework of a project aimed at finding novel predictive biomarkers of VOCs exposure-related diseases, the effect of exposure to ethylbenzene, toluene, and xylene has been analyzed in a group of painters (spray- and roller-painters) working in the shipyard industry. Airborne levels of solvents were higher in spray- than in roller-painters, and comparable to the Occupational Exposure Limits (OELs), particularly for toluene and xylene. The urinary concentration of each volatile organic compound (VOC) and of the corresponding metabolites were also concurrently measured. A set of oxidative stress biomarkers, i.e., the products of DNA and RNA oxidation, RNA methylation, and protein nitration, were measured, and found significantly higher at the end of the work shift. MicroRNA (MiRNA) expression was analyzed in the VOC-exposed workers and in a control group, finding 56 differentially expressed (DE) miRNAs at a statistically significant level (adjusted p ≤ 0.01). The Receiver-Operating Characteristic curves, computed for each identified miRNA, showed high sensitivity and specificity. A pathway analysis in the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that miRNA-1, which was found downregulated in exposed workers, is involved in the lung cancer oncogenesis. A subset of 10 miRNAs (out of the 56 DE) was selected, including those with the highest correlation to the urinary dose biomarkers measured at the end of work-shift. Multivariate ANOVA analysis showed a statistically significant correlation between the urinary dose biomarkers (both the VOCs urinary concentration and the VOCs' metabolite concentration), and the identified miRNA subset, indicating that the exposure to low VOC doses may be sufficient to activate the miRNA response. Four miRNAs belonging to the subset strongly related to the VOCs and VOCs' metabolites concentration were individuated, miR-589-5p, miR-941, miR-146b-3p and miR-27a-3p, with well-known implications in oxidative stress and inflammation processes.

A Predictive Model Assessing Genetic Susceptibility Risk at Workplace.

(1) Background: The study of susceptibility biomarkers in the immigrant workforce integrated into the social tissue of European host countries is always a challenge, due to high individual heterogeneity and the admixing of different ethnicities in the same workplace. These workers having distinct cultural backgrounds, beliefs, diets, and habits, as well as a poor knowledge of the foreign language, may feel reluctant to donate their biological specimens for the biomonitoring research studies. (2) Methods: A model predicting ethnicity-specific susceptibility based on principal component analysis has been conceived, using the genotype frequency of the investigated populations available in publicly accessible databases. (3) Results: Correlations among ethnicities and between ethnic and polymorphic genes have been found, and low/high-risk profiles have been identified as valuable susceptibility biomarkers. (4) Conclusions: In the absence of workers' consent or access to blood genotyping, ethnicity represents a good indicator of the subject's genotype. This model, associating ethnicity-specific genotype frequency with the susceptibility biomarkers involved in the metabolism of toxicants, may replace genotyping, ensuring the necessary safety and health conditions of workers assigned to hazardous jobs.

Circulating microRNAs as potential biomarkers of occupational exposure to low dose organic solvents.

Circulating microRNAs (miRNAs) have been recently acknowledged as novel and non-invasive biomarkers of exposure to environmental and occupational hazardous substances. This preliminary study investigates the potential role of blood miRNAs as molecular biomarkers of exposure to the most common organic solvents (ethylbenzene, toluene, xylene) used in the shipyard painting activity. Despite the low number of recruited workers, a two-tail standard Students' test with Holm-Bonferroni adjusted p-value shows a significant up-regulation of two miRNAs (miR_6819_5p and miR_6778_5p) in exposed workers with respect to controls. A correlation analysis between miRNA, differentially expressed in exposed workers and in controls and urinary dose biomarkers i.e. methylhyppuric acid (xylenes metabolite), phenylglyoxylic and mandelic acid (ethylbenzene metabolites) S-benzyl mercapturic acid (toluene metabolite) and S-phenylmercapturic acid (benzene metabolite) measured at the end of the work-shift, allowed the identification of high correlation (0.80-0.99) of specific miRNAs with their respective urinary metabolites. MiRNA_671_5p correlated with methylhippuric, S-phenylmercapturic and S-benzyl mercapturic acid while the miRNA best correlating with the phenylglioxylic acid was miRNA_937_5p. These findings suggest miRNA as sensitive biomarkers of low dose exposure to organic chemicals used at workplace. Urinary DNA and RNA repair biomarkers coming from the oxidation product of guanine have been also associated to the different miRNAs. A significant negative association was found between 8-oxo-7,8-dihydroguanine (8-oxoGua) urinary concentration and miR_6778_5p. The findings of the present pilot study deserve to be tested on a larger population with the perspective of designing a miRNA based test of low dose exposure to organic solvents.

Susceptibility biomarker detection in urine exfoliate DNA.

AIM: The occupational biomonitoring of exposures to carcinogens is carried out by measuring dose (metabolites) and susceptibility biomarkers (gene polymorphisms) in two biological matrices: urine for metabolite detection and blood for genotyping. Blood is the most common substrate but has some disadvantages including: invasiveness of the harvesting technique; need of specialized staff and equipment; and high infection risk. METHODS & RESULTS: We propose our in-house approach using urine as single sample in 20 volunteers for simultaneous detection of dose and susceptibility biomarkers in order to verify efficacy and feasibility. CONCLUSION: Despite the low number of subjects, interindividual and gender variability in DNA yield, urine genomic DNA is a valuable source for gene polymorphism studies when blood samples are not available. [Formula: see text].

Climate change impact on microclimate of work environment related to occupational health and productivity.

INTRODUCTION: Climate change is a global emergency that influences human health and occupational safety. Global warming characterized by an increase in temperature of the ambience and humidity affects human health directly impairing body thermoregulation with serious consequences: dehydration, fatigue, heat stroke and even death. Several studies have demonstrated negative effects of climate change on working populations in a wide variety of workplaces with particular regard to outdoor and uncooled indoor workplaces. Most vulnerable workers are outdoor workers in tropical and subtropical countries usually involved in heavy labor during hot seasons. Many of the consequences therefore, regarding working people are possible, even without health symptoms by reducing work productivity. AIM: The scope of this review is to investigate effects of climate change on workers both in relation to health and work productivity. METHODS: This study has been realized by analyzing recent international literature. CONCLUSIONS: In order to reduce negative effects of climate change on working populations it is essential to implement preventive measures with a multidisciplinary strategy limiting health risks and improving work productivity.

Is driving in a hot vehicle safe?

PURPOSE: This paper investigates the thermal conditions inside a passenger car driven after it was left a few hours in a shade-less parking lot, and the related implications for the driving performance. MATERIALS AND METHODS: Experimental results for twelve tests carried out in four different vehicles are presented and discussed. Each test is characterized by means of the predicted core temperature tcore of the driver after 60 minutes, as calculated by a heat stress model. The fractional performance loss is calculated by adjusting existing algorithms for office tasks to accommodate literature data on driving-related tasks, and then re-casting the algorithm as a function of tcore instead of the air temperature ta. RESULTS: Based on measured temperatures and humidities, fractional performance losses up to 50% are predicted even for relatively simple tasks such as keeping the vehicle on a straight course. Performance losses in excess of 75% are predicted, under the most extreme thermal conditions, for demanding tasks, such as correctly identifying a signal and reacting in due time. CONCLUSIONS: The implementation in technical standards on heat stress assessment of two new thresholds is recommended. The lower threshold, to be set at tcore ≅ 37.1 °C, is aimed at ensuring that the subject is able to carry out demanding mental tasks without appreciable performance loss, while the higher threshold, to be set at tcore ≅ 37.2 °C applies to simpler tasks.

Low occupational exposure to benzene in a petrochemical plant: modulating effect of genetic polymorphisms and smoking habit on the urinary t,t-MA/SPMA ratio.

The identification of reliable biomarkers is critical for the assessment of occupational exposure of benzene: S-phenylmercapturic acid (SPMA) and trans,trans-muconic acid (t,t-MA) are the most currently used. t,t-MA is an open-ring metabolite, but it is also a metabolite of the food preservative sorbic acid, while SPMA is formed by conjugation with glutathione, and several studies suggested that the genetic polymorphism of glutathione S-transferases modulates its production. This study compared the ability of these metabolites to assess the benzene exposure in a big group of petrochemical workers. Furthermore, investigated how genetic polymorphism of glutathione S-transferase theta 1 (GSTT1), glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase pi 1 (GSTP1) and smoking habits, may influence their excretion. Results showed that occupational exposure to benzene was negligible compared to that from smoking and confirmed the modulating effect of the genetic polymorphism of GSTT1 on the urinary excretion of SPMA, but not of t, t-MA, even at very low levels of benzene exposure. The same effect was found for GSTM1, but only for smokers. The t,t-MA/SPMA ratio was not a constant value and resulted to be higher than the corresponding Biological Exposure Index (BEI) ratio, which is currently equal to 20. Higher values of metabolite have been associated with the GSTT1 or GSTM1 null genotype and these are responsible for increase health risk. We suggest that this ratio could be used as a marker of individual susceptibility for subjects with benzene exposure.