Role of genetic variants and host polymorphisms on COVID-19: From viral entrance mechanisms to immunological reactions.

Coronavirus disease 2019 (COVID-19), caused by a highly pathogenic emerging virus, is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Knowledge regarding the pathogenesis of this virus is in infancy; however, investigation on the pathogenic mechanisms of the SARS-CoV-2 is underway. In COVID-19, one of the most remarkable characteristics is the wide range of disease manifestation and severity seen across individuals of different ethnic backgrounds and geographical locations. To effectively manage COVID-19 in the populations, beyond SARS-CoV-2 detection, serological response assessment, and analytic techniques, it is critical to obtain knowledge about at-risk individuals and comprehend the identified variations in the disease's severity in general and also in the populations' levels. Several factors can contribute to variation in disease presentation, including population density, gender and age differences, and comorbid circumstances including diabetes mellitus, hypertension, and obesity. Genetic factors presumably influence SARS-CoV-2 infection susceptibility. Besides this, COVID-19 has also been linked with a higher risk of mortality in men and certain ethnic groups, revealing that host genetic characteristics may affect the individual risk of death. Also, genetic variants involved in pathologic processes, including virus entrance into cells, antiviral immunity, and inflammatory response, are not entirely understood. Regarding SARS-CoV-2 infection characteristics, the present review suggests that various genetic polymorphisms influence virus pathogenicity and host immunity, which might have significant implications for understanding and interpreting the matter of genetics in SARS-CoV-2 pathogenicity and customized integrative medical care based on population investigation.

Polycyclic aromatic hydrocarbons exposures and telomere length: A cross-sectional study on preschool children.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with shorter telomere length (TL), a marker of ageing at cellular level. However, the available evidence on this association among children is still scarce. We therefore aimed to assess, the relationship between urinary 1-hydroxipayrene (1-OHP), a marker of exposure to PAHs, and relative leukocyte TL (LTL) in children at preschool age. Our study was based on 200 children enrolled from 27 randomly-selected kindergartens in the city of Sabzevar, Iran (2017). 1-OHP levels in the participants' urine samples were measured using solid phase extraction (SPE) method and high-performance liquid chromatography (HPLC). Moreover, real-time PCR was used to measure the LTL in the participants' blood samples. Linear mixed effects models, controlled for relevant covariates, were applied to investigate the association of 1-OHP concentration and LTL. The median (interquartile range (IQR)) of relative LTL and urinary 1-OHP were 0.83 (0.7) and 257 (375.5) ng/L, respectively. In the fully adjusted model, an IQR increase in urinary 1-OHP was related to -0.05 (95% confidence interval (CI): 0.09, -0.01, P-value = 0.02) decrease in relative LTL. This association was similar among boys and girls; however, we observed indications for a stronger association for those children whose parents had university education. Our study suggested an inverse relationship between urinary 1-OHP and LTL in children at preschool age. However, further longitudinal research with repeated measures of PAHs and LTL are needed to confirm these findings.

Maternal exposure to ambient particulate matter and green spaces and fetal renal function.

Exposure to air pollution has been associated with different harmful effects and exposure to greenspace has been related to improved human health. However, the available evidence on the impact of these exposures on renal function is still scarce. The aim of this study was to determine the relationship between exposure to ambient levels of PM1, PM2.5, PM10 and indicators of exposure to traffic as well as greenspace during pregnancy and fetal renal function based on the umbilical cord blood. This study was based on 150 pregnant women residing in Sabzevar, Iran (2018). Multiple linear regression models were developed to estimate the association of glomerular filtration rate (GFR), creatinine (Cr) and blood urea nitrogen (BUN) with exposure to air pollution, traffic, and greenspace (one at a time) controlled for relevant covariates. There was an inverse significant association between exposure to PM1, PM2.5, PM10 and total street length in a 100 m buffer around the home and eGFR. Increase in distance to major road and residential surrounding greenness (100 m buffer) was associated with increase in eGFR. We observed a significant direct association between exposure to PMs as well as street length in 100 m buffer and serum level of Cr. There was also an inverse association between distance to major road and NDVI in 100 m buffer and Cr. The associations for blood urea nitrogen (BUN) were not statistically significant. Our results suggest that exposure to air pollution during pregnancy could have negative impact and exposure to greenspace could have positive impact on renal function of fetal.

Novel Loss-of-Function Variants in CDC14A are Associated with Recessive Sensorineural Hearing Loss in Iranian and Pakistani Patients.

CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss.

Signaling roadmap to epithelial-mesenchymal transition in pterygium, TWIST1 centralized.

Pterygium as a complex disease shares common features with other malignant cells in its onset recurrence and especially epithelial-mesenchymal transition (EMT) transition. Although using different approaches including conjunctival autografts, amniotic membrane, radiotherapy, mitomycin C (MMC) has shown promising insights in the inhibition of pterygium recurrence, it needs to be investigated in more details in molecular pathways to present adjuvant target therapy. In this study, we aimed to evaluate the expression of and then illustrate the role of signaling pathways on EMT in pterygium. Using real-time polymerase chain reaction, the twist-related protein 1 (TWIST1) expression was compared in primary pterygium and normal conjunctiva. This study assessed the mRNA expression, as well as the association between the clinicopathological indices and the gene expression level. The expression level of TWIST1 was overexpressed in 36% of our cohort ( n = 76). There was a significant positive correlation between recurrence with grade T, grade V and a significant negative correlation with growth activity. Our vast literature review on different signaling pathways in pterygium showed that EMT has centralization role in recurrence of this disease. Our data confirmed that EMT is important in the recurrence of pterygium samples and different signaling pathways end up activating the EMT markers. It is suggested to evaluate the environmental factors and their correlation with molecular markers to select favorable treatment for this kind of diseases.

ABCG2, SCN1A and CYP3A5 genes polymorphism and drug-resistant epilepsy in children: A case-control study.

PURPOSE: Drug Resistant -Epilepsy is still a major challenge in pharmacotherapy of epilepsy. Pharmacogenetic pathways are one of the most important elements that can help clinicians determine medication response and provide more efficient drug therapy, especially in cases of drug resistance. Genetic alterations in drug target and transporter proteins, in part, could explain the development of drug-resistant epilepsy. We sought to assess the association of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) candidate polymorphisms with drug-resistant epilepsy among Iranian children with epilepsy. METHODS: In a hospital-based case-control study, 93 participants, including 45 men and 48 women aged 1.5 to 14 years old were recruited. Genotyping of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) polymorphisms using the high-resolution melting (HRM) method were measured in 46 children with drug-resistant epilepsy and 47 healthy control subjects. The binary logistic regression model was used to estimate the odds ratio (OR) for each polymorphism per effect allele increase. RESULTS: The mean (standard deviation [SD]) age of the drug-resistant patients was 10.7 (9.0) years versus 7.3 (3.6) in the control group. In the case group, most of the patients with epilepsy were diagnosed with generalized seizure (about 87%) and negative epileptic history status (63%). Furthermore, idiopathic epilepsy was dominant in the case group (69%). There was a clinically meaningful increase in the chance of drug-resistant epilepsy in participants with candidate polymorphism in ABCG2 gene (per allele T increase, adjusted odds ratio [OR] 2.41, confidence interval [CI] 0.99 to 5.87, P=0.05). No significant association was found between CYP3A5 (per allele C increase, OR 0.92, CI 0.33 to 2.60, P= 0.88) and SCN1A (per allele *1 increase, OR 0.65, 95% CI 0.34 to 1.23, P= 0.19) with drug-resistant epilepsy. CONCLUSION: We found evidence for the relationship between the ABCG2 gene polymorphism and a higher chance of drug-resistant epilepsy in children. This finding may have important implications for understanding the role of ABCG2 gene polymorphism in children with drug-resistant epilepsy.

Green space exposure during pregnancy and umbilical cord blood levels of liver enzymes.

Evidence has suggested better pregnancy outcomes due to exposure to greenspace; however, the studies on such an association with the level of liver enzymes in the cord blood are still nonexistent. Hence, this study investigated the relationship between exposure to greenspace during the entire pregnancy and gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in cord blood samples. We selected 150 pregnant women from our pregnancy cohort in Sabzevar, Iran (2018). Greenspace exposure was characterized based on (i) residential distance to green space, (ii) time spent in public/private green spaces, (iii) residential surrounding greenspace, (iv) visual access to greenspace, and (v) number of indoor natural pot plants at home. We developed linear regression models to investigate the adjusted associations of greenspace exposure with enzyme levels. Each one interquartile range (IQR) increase in the residential surrounding greenspace (100 m buffer) was related to a reduction of -12.58 (U/L) (95% CI -22.86, -2.29), -3.35 (U/L) (95% CI -5.50, -1.20), and -0.57 (U/L) (95% CI -1.12, -0.02) in the levels of GGT, AST, and ALT, respectively. Moreover, a similar association was observed for the time the participants spent in green spaces. A decrease in the residential distance to large green spaces was related with lower cord blood levels of AST, ALT, and GGT. Having a window with greenspace view at home was significantly related to lower AST level. The results for the indoor plant pots were not conclusive. Our findings suggested an inverse relationship between greenspace exposure during pregnancy and cord blood levels of liver enzymes. Further studies in other settings and populations are needed to confirm our findings.

Determinants of carbon load in airway macrophages in pregnant women.

The airway macrophages carbon loading (AMCL) has been suggested to be a biomarker of the long-term exposure to air pollution; however, to date no study has characterized AMCL for the pregnancy period. Therefore, this study aimed to assess the determinants of AMCL during pregnancy in Iran, a middle-income country. This study was based on a sample of 234 pregnant women with term and normal vaginal delivery who were residing in Sabzevar, Iran (2019). We characterized 35 potential determinants of personal exposure to air pollution for each participant, including six personal, nine indoor, and 20 home-outdoor factors. We applied Deletion/Substitution/Addition algorithm to identify the most relevant determinants that could predict AMCL levels. The median (IQR) of AMCL level was 0.12 (0.30) µm2 with a successful sputum induction in 82.9% (194) of participants. Ambient residential PM2.5 levels were positively associated with higher AMCL levels. On the other hand, increased residential distance to the traffic lights, squares and ring-roads, the duration of opening window per day, and opening window during cooking were inversely associated with AMCL levels. Our findings provide novel insights on the different personal, indoor, and outdoor determinants of personal exposure to air pollution during pregnancy in a middle-income country.

Maternal exposure to ambient air pollution during pregnancy and lipid profile in umbilical cord blood samples; a cross-sectional study.

Adverse health effects of exposure to air pollution have been investigated in many previous studies. However, there is no study available on the association between maternal exposure to air pollution during pregnancy and cord blood lipid profile. This study, based on 150 mother-newborn pairs residing in Sabzevar, Iran (2018), evaluated the association of exposure to ambient air pollution as well as traffic indicators (total street length in different buffers around residential address and distance to major roads) during entire pregnancy with lipid levels cord blood lipid profile. Concentrations of PM10, PM2.5, and PM1 at maternal residential address were estimated using land use regression (LUR) models. We measured triglyceride (TAG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) levels and TC/HDL-C and TAG/HDL-C ratio in the cord blood samples to characterize their lipid profile. Multiple linear regression models were developed to estimate the association of exposure to air pollution and traffic indicators with cord blood lipid profile controlled for relevant covariates. Higher concentrations of PM2.5 and PM10 were associated with higher levels of TAG, TC, HDL-C, TC/HDL-C, and TAG/HDL-C in cord blood samples. Moreover, higher concentration of PM1 was associated with higher levels of TAG, TC and LDL-C. There was also a positive association between total street length in 100 m buffer around home and serum levels of TC, TAG, LDL-C and TC/HDL ratio (ß = 3.73, 95% confidence intervals (CI): 1.76, 5.71; ß = 2.75, 95% CI: 0.97, 4.53; ß = 1.87, 95% CI: 0.64, 3.09; ß = 0.06, 95% CI: 0.01, 0.11, respectively). However, the associations for total street length in larger buffers and distance to major roads were not statistically significant. Our findings support a relationship between exposure to air pollution during pregnancy and increase in cord blood lipid levels.

Exposure to air pollution during pregnancy and newborn liver function.

Exposure to air pollution has been associated with a wide range of adverse health outcomes. However, the available evidence on the impact of air pollution exposures on liver enzymes is still scarce. The aim of the present study was to assess the relationship between exposure to ambient PM1, PM2.5 and PM10 during pregnancy and serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) in cord blood samples of newborns. Moreover, the association between total street length in different buffers and distance to major roads at the maternal residential address and liver enzymes were investigated. This cross-sectional study was based on data from a sample of 150 newborns, from Sabzevar, Iran. Land use regression models were used to estimate concentrations of air pollutants at home during pregnancy. Multiple linear regression was developed to estimate association of AST, ALT, ALP and GGT with air pollution controlled for relevant covariates. In fully adjusted models, increase in PM1 and PM2.5 as well as PM10 were associated with higher levels of AST, ALT and GGT. Moreover, there was a significant association between total street length in a 100 m buffer at residential address with AST, ALT and GGT. Each meter increase in distance to major roads was associated with -0.017 (95% confidence interval (CI): -0.028, -0.006) decrease in AST. Overall, our findings were supportive for association between PMs exposure during pregnancy and increase in liver enzymes in newborns. Further studies are needed to confirm these findings in other settings and populations.

Spatial distribution variation and probabilistic risk assessment of exposure to chromium in ground water supplies; a case study in the east of Iran.

A high concentration of chromium (VI) in groundwater can threaten the health of consumers. In this study, the concentration of chromium (VI) in 18 drinking water wells in Birjand, Iran, s was investigated over a period of two yearsNon-carcinogenic risk assessment, sensitivity, and uncertainty analysis as well as the most important variables in determining the non-carcinogenic risk for three age groups including children, teens, and adults, were performed using the Monte Carlo simulations technique. The northern and southern regions of the study area had the highest and lowest chromium concentrations, respectively. The chromium concentrations in 16.66% of the samples in an area of 604.79 km2 were more than World Health Organization (WHO) guideline (0.05 mg/L). The Moran's index analysis showed that the distribution of contamination is a cluster. The Hazard Index (HI) values for the children and teens groups were 1.02 and 2.02, respectively, which was more than 1. A sensitivity analysis indicated that the most important factor in calculating the HQ was the concentration of chromium in the consumed water. HQ values higher than 1 represent a high risk for the children group, which should be controlled by removing the chromium concentration of the drinking water.