Differential Expression of Serum Proinflammatory Cytokine TNF-α and Genetic Determinants of TNF-α, CYP2C19*17, miR-423 Genes and Their Effect on Coronary Artery Disease Predisposition and Progression.

Coronary artery disease (CAD) is the leading cause of death and hospitalization worldwide and represents a problem for public health systems everywhere. In Saudi Arabia, the prevalence of CAD is estimated to be 5.5%. Risk factors for CAD include older age, male gender, obesity, high blood pressure, smoking, diabetes, hyperlipidemia, and genetic factors. Reducing the risk factors in susceptible individuals will decrease the prevalence of CAD. Genome wide association studies have helped to reveal the association of many loci with diseases like CAD. In this study, we examined the link between single nucleotide variations (SNVs) of TNF-α-rs1800629 G>A, CYP2C19*17 (rs12248560) C>T, and miR-423 rs6505162 C>A and the expression of TNF-α with CAD. We used the mutation specific PCR, ARMS-PCR, and ELISA. The results showed that the A allele of the TNF-α rs1800629 G>A SNP is linked to CAD with odd ratio (OR) (95% CI) = 2.10, p-value = 0.0013. The T allele of the CYP2C19*17 (rs12248560) C>T is linked to CAD with OR (95% CI) = 2.02, p-value = 0.003. In addition, the A allele of the miR-423 rs6505162 C>A SNV is linked to CAD with OR (95% CI) = 1.49, p-value = 0.036. The ELISA results indicated that the TNF-α serum levels are significantly increased in CAD patients compared to healthy controls. We conclude the TNF-α rs1800629 G>A, CYP2C19*17, and miR-423 rs6505162 C>A are potential genetic loci for CAD in the Saudi population. These findings require further verification in future studies. After being verified, our results might be utilized in genetic testing to identify individuals that are susceptible to CAD and, therefore, for whom reducing modifiable risk factors (e.g., poor diet, diabetes, obesity, and smoking) would result in prevention or delay of CAD.

Genetic Determinants of Cardiovascular Disease: The Endothelial Nitric Oxide Synthase 3 (eNOS3), Krüppel-Like Factor-14 (KLF-14), Methylenetetrahydrofolate Reductase (MTHFR), MiRNAs27a and Their Association with the Predisposition and Susceptibility to Coronary Artery Disease.

Coronary artery disease (CAD) is an important cause of death worldwide. CAD is caused by genetic and other factors including hypertension, hyperlipidemia, obesity, stress, unhealthy diet, physical inactively, smoking and Type 2 diabetes (T2D). The genome wide association studies (GWASs) have revealed the association of many loci with risk to diseases such as cancers, T2D and CAD. Nitric oxide (NO) is a potent vasodilator and is required for normal vascular health. It is produced in the endothelial cells in a reaction catalyzed by the endothelial NO synthase (eNOS). Methylenetetrahydrofolate reductase (MTHFR) is a very important enzyme involved in metabolism of folate and homocysteine, and its reduced function leads to cardiovascular disease. The Krüppel-like factor-14 (KLF-14) is an important transcriptional regulator that has been implicated in metabolic syndrome. MicroRNA (MiRNAs) are short non-coding RNAs that regulate the gene expression of proteins involved in important physiological processes including cell cycle and metabolism. In the present study, we have investigated the potential impact of germline pathogenic variants of endothelial eNOS, KLF-14, MTHFR, MiRNA-27a and their association with risk to CAD in the Saudi population. Methods: Amplification Refractory Mutation System (ARMS) PCR was used to detect MTHFR, KLF-14, miRNA-27a and eNOS3 genotyping in CAD patients and healthy controls. About 125 CAD cases and 125 controls were enrolled in this study and statistical associations were calculated including p-value, risk ratio (RR), and odds ratio (OD). Results: There were statistically significant differences (p < 0.05) in genotype distributions of MTHFR 677 C>T, KLF-14 rs972283 G>A, miRNAs27a rs895819 A>G and eNOS3 rs1799983 G>T between CAD patients and controls. In addition, our results indicated that the MTHFR-TT genotype was associated with increased CAD susceptibility with an OR 2.75 (95%) and p < 0.049, and the KLF14-AA genotype was also associated with increased CAD susceptibility with an OR of 2.24 (95%) and p < 0.024. Moreover, the miRNAs27a-GG genotype protects from CAD risk with an OR = 0.31 (0.016), p = 0.016. Our results also indicated that eNOS3 -GT genotype is associated with CAD susceptibility with an OR = 2.65, and p < 0.0003. Conclusion: The MTHFR 677C>T, KLF14 rs972283 G>A, miRNAs27a A>G, and eNOS3 rs1799983 G>T genotypes were associated with CAD susceptibility (p < 0.05). These findings require verification in future large-scale population based studies before these loci are used for the prediction and identification of individuals at risk to CAD. Weight control, physical activity, and smoking cessation are very influential recommendations given by clinicians to the at risk individuals to reduce or delay the development of CAD.

Effective options for addressing air quality- related environmental public health burdens in Saudi Arabia.

Air pollution poses major disease burdens globally and accounts for approximately 10% of deaths annually through its contribution to a variety of respiratory, cardiovascular, and other diseases. The burden of disease is particularly acute in Saudi Arabia, where a mix of anthropogenic and natural sources of air pollution threatens public health. Addressing these burdens requires careful study of the costs and effectiveness of available technologies and policies for reducing emissions (mitigation) and avoiding exposure (adaptation). To help evaluate these options, we conduct a semi-systematic literature review of over 3,000 articles published since 2010 that were identified by searches of literature focused on pollution mitigation and pollution adaptation. We identify a wide variety of effective mitigation and adaptation technologies and find that cost-effectiveness information for policy design is highly variable in the case of mitigation, both within and across pollution source categories; or scarce, in the case of adaptation. While pollution control costs are well studied, policy costs differ; these may vary more by location because of factors such as technology operating conditions and behavioral responses to adaptation initiatives, limiting the generalizability of cost-effectiveness information. Moreover, potential cost advantages of multipollutant control policies are likely to depend on the existing mix of pollution sources and controls. While the policy literature generally favors more flexible compliance mechanisms that increase the cost of polluting to reflect its costs to society, important policy design factors include policy co-benefits, distributional concerns, and inter-regional harmonization. In addition to these key themes, we find that further study is needed both to improve the availability of cost information for adaptation interventions and to localize technology and policy cost estimates to the Saudi context.

Clinical Utility of Amplification Refractory Mutation System-Based PCR and Mutation-Specific PCR for Precise and Rapid Genotyping of Angiotensin-Converting Enzyme 1 (ACE1-rs4646996 D>I) and Angiotensin-Converting Enzyme 2 (ACE2-rs4240157T>C) Gene Variations in Coronary Artery Disease and Their Strong Association with Its Disease Susceptibility and Progression

Background: Experimental clinical and research studies demonstrated that the renin−angiotensin system (RAS) affects the pathogenesis of atherosclerosis and the prognosis of coronary heart disease (CHD). The results show that ACE2 (angiotensin I-converting enzyme 2) might act as a protective protein for cardiovascular diseases; however, only a few studies in human populations have been carried out. The aim of this study was to develop, optimize, and validate a direct T-ARMS-based PCR assay for the precise and rapid genotyping of ACE1-rs4646996 D>I and ACE2-rs4240157T>C and study their association with coronary artery disease susceptibility and progression. Methodology: This study included 149 consecutive coronary artery disease patients and 150 healthy controls. We utilized T-ARMS for the precise and rapid genotyping of ACE2-rs4240157; rs4646994. Results: Our results indicated that the ACE1-rs4646996 D>I genotypes observed between CAD cases and controls were statistically significant (p < 0.008) and, similarly, the ACE2-rs4240157T>C genotypes observed were significant (p < 0.0001). Moreover, the frequency of the D allele (ACE1-D>I) and C allele (ACE2-rs4240157T>C) was found to be higher among CAD patients than the HC. Our results indicated that in the codominant model, the ACE2-ID genotype was strongly associated with increased CAD susceptibility in a codominant model with an OR of 2.37, (95%) CI = (1.023−5.504), and p < 0.04. Similarly, the ACE2-DD genotype was strongly associated with an increased CAD susceptibility with an OR of 3.48, (95%) CI = (1.49 to 8.117), and p < 0.003. Similarly, in allelic comparison, the D allele was strongly associated with CAD susceptibility with an OR of 1.59, (95%) CI = (1.12−2.24), and p < 0.003. Our results revealed that there was a significant correlation between ACE2-I/D genotypes and hypertension, T2D, and obesity (p < 0.05). The results of ACE2 rs4240157 genotyping indicated a strong association in the codominant model with an increased CAD susceptibility with an OR of 3.62, (95%) CI = (2.027 to 6.481), and p < 0.0001. Similarly, in a dominant inheritance model, a strong association is observed between the ACE2 rs4240157 (CT+CC) genotype with an OR of 6.34, (95%) CI = (3.741 to 10.749), and p < 0.0001. In allelic comparison, the T allele was strongly associated with CAD susceptibility with an OR of 5.56, (95% CI = (3.56 to 7.17), and p < 0.0001. Similarly, our results revealed that there was a significant association of the ACE2-rs4240157T>C genotypes with Triglycerides (mg/dL), HDL-C (mg/dL), total Cholesterol (mg/dL), and C-reactive protein (mg/L) in CAD. Conclusion: It was indicated that the ARMS technique and MS-PCR assay proved to be fast, accurate, and reliable for ACE2-rs4240157T>C and ACE1-rs4646996 D>I, respectively, and can be used as a potential molecular tool in the diagnosis of genetic diseases in undeveloped and developing countries­where there might be a shortage of medical resources and supplies. ACE1-I>D genotypes were strongly associated with T2D, hypertension, and obesity (p < 0.002). Besides the ACE2-rs4240157 CT heterozygosity genotype, the T allele was strongly associated with CAD susceptibility. Future longitudinal studies in different ethnic populations with larger sample sizes are recommended to validate these findings

Epidemiology of childhood injuries in Saudi Arabia: a scoping review.

BACKGROUND: Injury is the leading cause of death among Saudi children. Despite that, much remains unknown on the epidemiology and the extent of burden. This scoping review aims to describe previous literature on injury burden, including types, causes, and outcomes. METHODS: We conducted a scoping literature search of English published articles on injuries among Saudi children between 0 to 18 years old using Scopus, MEDLINE, and Web of Science between January 2000 and December 2020. The primary outcome was the type and the cause of childhood injuries. Data extraction was based on specified data elements that included study characteristics and epidemiological parameters. The STROBE checklist was used to assess the quality of publications. RESULTS: The initial review identified 3,384 studies. Of which, 36 studies met the inclusion criteria. A total of 20,136 children were included; of them, 69% were males. Among studies that examined overall injuries, falls represented 31.9%, while 25.1% were due to Motor Vehicle Collision (MVC). The leading cause of fractures was falls (37.9%), followed by MVC (21.5%). The leading cause was flames (52.1%) followed by scald (36.4%) for burns. While for poisoning, medications were the leading cause of (39.9%), followed by toxic household products (25.7%). Weighted mortality rates were 5.2% for overall injuries, 8.3% for fractures of the skull and spine, and 17.4% for burns. CONCLUSIONS: MVC and falls are associated with the highest share of injuries in the kingdom. These findings can guide prevention efforts to reduce injury burden and improve population health. Further population-based research is warranted to explore the determinants of childhood injuries across all regions of Saudi Arabia.

Role of Selected miRNAs as Diagnostic and Prognostic Biomarkers in Cardiovascular Diseases, Including Coronary Artery Disease, Myocardial Infarction and Atherosclerosis.

Cardiovascular diseases are the leading cause of death worldwide in different cohorts. It is well known that miRNAs have a crucial role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. MiRNAs also have been reported to be associated with cardiac reactions, leading to myocardial infarction (MCI) and ultimately heart failure (HF). To prevent these heart diseases, proper and timely diagnosis of cardiac dysfunction is pivotal. Though there are many symptoms associated with an irregular heart condition and though there are some biomarkers available that may indicate heart disease, authentic, specific and sensitive markers are the need of the hour. In recent times, miRNAs have proven to be promising candidates in this regard. They are potent biomarkers as they can be easily detected in body fluids (blood, urine, etc.) due to their remarkable stability and presence in apoptotic bodies and exosomes. Existing studies suggest the role of miRNAs as valuable biomarkers. A single biomarker may be insufficient to diagnose coronary artery disease (CAD) or acute myocardial infarction (AMI); thus, a combination of different miRNAs may prove fruitful. Therefore, this review aims to highlight the role of circulating miRNA as diagnostic and prognostic biomarkers in cardiovascular diseases such as coronary artery disease (CAD), myocardial infarction (MI) and atherosclerosis.

Environmental Risk Factors and Health: An Umbrella Review of Meta-Analyses.

Background: Environmental health is a growing area of knowledge, continually increasing and updating the body of evidence linking the environment to human health. Aim: This study summarizes the epidemiological evidence on environmental risk factors from meta-analyses through an umbrella review. Methods: An umbrella review was conducted on meta-analyses of cohort, case-control, case-crossover, and time-series studies that evaluated the associations between environmental risk factors and health outcomes defined as incidence, prevalence, and mortality. The specific search strategy was designed in PubMed using free text and Medical Subject Headings (MeSH) terms related to risk factors, environment, health outcomes, observational studies, and meta-analysis. The search was limited to English, Spanish, and French published articles and studies on humans. The search was conducted on September 20, 2020. Risk factors were defined as any attribute, characteristic, or exposure of an individual that increases the likelihood of developing a disease or death. The environment was defined as the external elements and conditions that surround, influence, and affect a human organism or population's life and development. The environment definition included the physical environment such as nature, built environment, or pollution, but not the social environment. We excluded occupational exposures, microorganisms, water, sanitation and hygiene (WASH), behavioral risk factors, and no-natural disasters. Results: This umbrella review found 197 associations among 69 environmental exposures and 83 diseases and death causes reported in 103 publications. The environmental factors found in this review were air pollution, environmental tobacco smoke, heavy metals, chemicals, ambient temperature, noise, radiation, and urban residential surroundings. Among these, we identified 65 environmental exposures defined as risk factors and 4 environmental protective factors. In terms of study design, 57 included cohort and/or case-control studies, and 46 included time-series and/or case-crossover studies. In terms of the study population, 21 included children, and the rest included adult population and both sexes. In this review, the largest body of evidence was found in air pollution (91 associations among 14 air pollution definitions and 34 diseases and mortality diagnoses), followed by environmental tobacco smoke with 24 associations. Chemicals (including pesticides) were the third larger group of environmental exposures found among the meta-analyses included, with 19 associations. Conclusion: Environmental exposures are an important health determinant. This review provides an overview of an evolving research area and should be used as a complementary tool to understand the connections between the environment and human health. The evidence presented by this review should help to design public health interventions and the implementation of health in all policies approach aiming to improve populational health.

Short-term effects of air pollution on daily asthma-related emergency department visits in an industrial city.

BACKGROUND: Epidemiological studies from Europe and North America have provided evidence that exposure to air pollution can aggravate symptoms in asthmatic patients. METHODS: Daily number of AEDv, air pollution levels (PM10, PM2.5, SO2, NO2 and CO) and meteorological variables was obtained from Jubail Industrial City, Saudi Arabia, for the period of 2007-11. Data were analyzed using a time-series approach. Relative risks (RRs) were estimated using Poisson regression. RESULTS: The associations between AEDv and PM10, PM2.5, SO2 and NO2 remained positive and statistically significant after mutual adjustment in the multi-pollutant model.The RR of AEDv increased by 5.4, 4.4, 3.4 and 2.2% per an inter-quartile range increase in SO2 (2.0 ppb), PM2.5 (36 µg/m3), NO2 (7.6 ppb) and PM10 (140 µg/m3), respectively. No significant associations between AEDv and CO were found. CONCLUSIONS: Current levels of ambient air pollution are associated with AEDv in this industrial setting in the Middle East. Greater awareness of environmental health protection and the implementation of effective measures to improve the quality of air in such settings would be beneficial to public health.