Single Nucleotide Variants (SNVs) of the Mesocorticolimbic System Associated with Cardiovascular Diseases and Type 2 Diabetes: A Systematic Review.

The mesocorticolimbic (MCL) system is crucial in developing risky health behaviors which lead to cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Although there is some knowledge of the MCL system genes linked to CVDs and T2D, a comprehensive list is lacking, underscoring the significance of this review. This systematic review followed PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The PubMed and Web of Science databases were searched intensively for articles related to the MCL system, single nucleotide variants (SNVs, formerly single nucleotide polymorphisms, SNPs), CVDs, T2D, and associated risk factors. Included studies had to involve a genotype with at least one MCL system gene (with an identified SNV) for all participants and the analysis of its link to CVDs, T2D, or associated risk factors. The quality assessment of the included studies was performed using the Q-Genie tool. The VEP and DAVID tools were used to annotate and interpret genetic variants and identify enriched pathways and gene ontology terms associated with the gene list. The review identified 77 articles that met the inclusion criteria. These articles provided information on 174 SNVs related to the MCL system that were linked to CVDs, T2D, or associated risk factors. The COMT gene was found to be significantly related to hypertension, dyslipidemia, insulin resistance, obesity, and drug abuse, with rs4680 being the most commonly reported variant. This systematic review found a strong association between the MCL system and the risk of developing CVDs and T2D, suggesting that identifying genetic variations related to this system could help with disease prevention and treatment strategies.

A Transcriptomic Analysis of Smoking-Induced Gene Expression Alterations in Coronary Artery Disease Patients.

Smoking is a well established risk factor for coronary artery disease (CAD). Despite this, there have been no previous studies investigating the effects of smoking on blood gene expression in CAD patients. This single-centre cross-sectional study was designed with clearly defined inclusion criteria to address this gap. We conducted a high-throughput approach using next generation sequencing analysis with a single-end sequencing protocol and a read length of 75-cycles. Sixty-one patients with a median age of 67 years (range: 28-88 years) were recruited, and only 44 subjects were included for further analyses. Our investigation revealed 120 differentially expressed genes (DEGs) between smokers and nonsmokers, with a fold change (FC) of ≥1.5 and a p-value < 0.05. Among these DEGs, 15 were upregulated and 105 were downregulated. Notably, when applying a more stringent adjusted FC ≥ 2.0, 31 DEGs (5 upregulated, annotated to immune response pathways, and 26 downregulated, involving oxygen and haem binding or activity, with FDR ≤ 0.03) remained statistically significant at an alpha level of <0.05. Our results illuminate the molecular mechanisms underlying CAD, fortifying existing epidemiological evidence. Of particular interest is the unexplored overexpression of RCAN3, TRAV4, and JCHAIN genes, which may hold promising implications for the involvement of these genes in CAD among smokers.

A systematic review and meta-analysis on the prevalence and impact of coronary artery disease in hospitalized COVID-19 patients.

Background: COVID-19 accounts for more than half a billion deaths globally. The clinical manifestations may vary in due course. Despite several studies aimed at determining the extent to which the disease's severity and mortality remain high when combined with other comorbidities, more research is required. Therefore, this review aimed to measure the pooled prevalence of coronary artery disease (CAD) among COVID-19 patients, specifically those with a history of CAD. Additionally, we aim to assess the association between mortality due to CAD and the severity of COVID-19 among hospitalized patients. Method: A comprehensive search in PubMed, Web of Science, the Cochrane Library, and the WHO COVID-19 database was conducted. English studies with original data on CAD, mortality, and ARDS among COVID-19 patients were included. PRISMA guidelines were followed. Results: Among the 2007 identified articles, 76 studies met the inclusion criteria. The pooled prevalence of CAD among COVID-19 patients was 14.4%(95% CI: 12.7-16.2). The highest prevalence was observed in European studies at 18.2%(95% CI: 13.3-24.2), while the lowest was in Asian studies at 10.4% (95% CI: 6.4-16.3). Participants with concurrent CAD at the time of hospital admission had twice the odds of mortality due to COVID-19 (2.64 [95% CI: 2.30-3.04]) with moderate heterogeneity (I2 = 45%, p < 0.01). Hospitalized COVID-19 patients with CAD had a 50% higher risk of ARDS (95% CI: 0.62-3.66), but this difference was not statistically significant. Conclusion: Although our analysis revealed evidence for a relationship between concurrent CAD at the time of hospital admission and mortality from COVID-19, however, global variation in health infrastructure, limitations of data reporting, and the effects of emerging variants must be considered in future investigations.

A combination of strongly associated prothrombotic single nucleotide polymorphisms could efficiently predict venous thrombosis risk.

Background: Venous thrombosis (VT) is multifactorial trait that contributes to the global burden of cardiovascular diseases. Although abundant single nucleotide polymorphisms (SNPs) provoke the susceptibility of an individual to VT, research has found that the five most strongly associated SNPs, namely, rs6025 (F5 Leiden), rs2066865 (FGG), rs2036914 (F11), rs8176719 (ABO), and rs1799963 (F2), play the greatest role. Association and risk prediction models are rarely established by using merely the five strongly associated SNPs. This study aims to explore the combined VT risk predictability of the five SNPs and well-known non-genetic VT risk factors such as aging and obesity in the Hungarian population. Methods: SNPs were genotyped in the VT group (n = 298) and control group (n = 400). Associations were established using standard genetic models. Genetic risk scores (GRS) [unweighted GRS (unGRS), weighted GRS (wGRS)] were also computed. Correspondingly, the areas under the receiver operating characteristic curves (AUCs) for genetic and non-genetic risk factors were estimated to explore their VT risk predictability in the study population. Results: rs6025 was the most prevalent VT risk allele in the Hungarian population. Its risk allele frequency was 3.52-fold higher in the VT group than that in the control group [adjusted odds ratio (AOR) = 3.52, 95% CI: 2.50-4.95]. Using all genetic models, we found that rs6025 and rs2036914 remained significantly associated with VT risk after multiple correction testing was performed. However, rs8176719 remained statistically significant only in the multiplicative (AOR = 1.33, 95% CI: 1.07-1.64) and genotypic models (AOR = 1.77, 95% CI: 1.14-2.73). In addition, rs2066865 lost its significant association with VT risk after multiple correction testing was performed. Conversely, the prothrombin mutation (rs1799963) did not show any significant association. The AUC of Leiden mutation (rs6025) showed better discriminative accuracy than that of other SNPs (AUC = 0.62, 95% CI: 0.57-0.66). The wGRS was a better predictor for VT than the unGRS (AUC = 0.67 vs. 0.65). Furthermore, combining genetic and non-genetic VT risk factors significantly increased the AUC to 0.89 with statistically significant differences (Z = 3.924, p < 0.0001). Conclusions: Our study revealed that the five strongly associated SNPs combined with non-genetic factors could efficiently predict individual VT risk susceptibility. The combined model was the best predictor of VT risk, so stratifying high-risk individuals based on their genetic profiling and well-known non-modifiable VT risk factors was important for the effective and efficient utilization of VT risk preventive and control measures. Furthermore, we urged further study that compares the VT risk predictability in the Hungarian population using the formerly discovered VT SNPs with the novel strongly associated VT SNPs.

Relationship between job stress and work-related quality of life among emergency medical technicians: a cross-sectional study.

OBJECTIVE: This study was aimed to determine the relationship between job stress and work-related quality of life (WRQoL) among emergency medical technicians (EMTs) in Lorestan province, Western Iran. DESIGN: This was a cross-sectional study. METHODS: Totally 430 EMTs who had been engaged in their respective units for more than 6 months from all emergency facilities in Lorestan province were selected using single stage cluster sampling method. Data were collected from April to July 2019 using two standard questionnaires: job stress (Health and Safety Executive (HSE)) and WRQoL. The OR with 95% CI was used to declare the statistical association (p≤0.05). RESULTS: All participants were exclusively males, with a mean age of 32±6.87 years. The overall average score of job stress using the HSE scale was 2.69±0.43; while the overall quality of working life score was 2.48±1.01. The type of working shift was found to have a significant impact on the HSE-average score (F(3,417)=5.26, p=0.01); and on the WRQoL-average score (F(3,417)=6.89, p<0.01). CONCLUSION: Two-thirds of EMTs working in governmental hospitals had job stress and a low quality of work-related life. Additionally, work shift was statistically significant associated with EMTs' job stress and WRQoL.

The Higher Prevalence of Venous Thromboembolism in the Hungarian Roma Population Could Be Due to Elevated Genetic Risk and Stronger Gene-Environmental Interactions.

Background: Interactions between genetic and environmental risk factors (GxE) contribute to an increased risk of venous thromboembolism (VTE). Understanding how these factors interact provides insight for the early identification of at-risk groups within a population and creates an opportunity to apply appropriate preventive and curative measures. Objective: To estimate and compare GxE for VTE risk in the general Hungarian and Roma populations. Methods: The study was based on data extracted from a database consisting of results previously obtained from a complex health survey with three pillars (questionnaire-based, physical, and laboratory examinations) involving 406 general Hungarian and 395 Roma subjects. DNA was genotyped for rs121909567 (SERPINC1), rs1799963 (F2), rs2036914 (F11), rs2066865 (FGG), rs6025 (F5), and rs8176719 (ABO) polymorphisms. After allele frequency comparisons, the odds ratio (OR) was calculated for individual SNPs. Furthermore, genetic risk scores (weighted GRS, unweighted GRS) were computed to estimate the joint effect of the genetic factors. Multivariable linear regression analysis was applied to test the impact of GxE on VTE risk after interaction terms were created between genetic and VTE risk factors [diabetes mellitus (DM), cancer, chronic kidney diseases (CKD), coronary artery diseases (CAD), migraine, depression, obesity, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein (HDL-C), triglyceride (TG), and smoking]. Results: Interestingly, the rs121909567 (SERPINC1, ATBp3 mutation) SNP was not present in the general population at all. However, the risk allele frequency was 1% among the Roma population, which might suggest a founder effect in this minority. This polymorphism multiplicatively interacted with CAD, CKD, cancer, DM, depression, migraine, and obesity. Even though interactions were not statistically significant, the trend of interaction showed the probability of an incremental VTE risk among the Roma population. The risk of VTE was 4.7 times higher (p > 0.05) for Roma subjects who had ≥3 wGRS (median value) compared with individuals having lower wGRS values but lower for the general subjects (OR = 3.1 × 10-8). Additionally, the risk of VTE was 6.6 times higher in the Roma population that had ≥3 risk alleles (median value) than in individuals with the 0-1 risk allele, and the overall risk was much higher for the Roma population (OR = 6.6; p > 0.05) than for the general Hungarian population (OR = 1.5; p > 0.05). Five positive and significant GxE interactions were identified in the Roma population. The risk of VTE was higher among depressive Roma subjects who carried the risk variant rs2036914 (ß = 0.819, p = 0.02); however, this interaction was not significant for the general subjects. The joint presence of high levels of LDL-C and rs2066865 (FGG) increased the VTE risk only among Roma individuals (ß = 0.389, p = 0.002). The possibility of VTE risk increment, as a result of a multiplicative interaction between rs8176719 (ABO) and cancer, was identified, which was higher for the Roma population (ß = 0.370, p < 0.001) than for the general population (ß = -0.042, p = 0.6). The VTE risk increased in the Roma population (ß = 0.280, p = 0.001), but was higher in the general population (ß = 0.423, p = 0.001) as a result of the multiplicative interaction between CAD and rs2036914 (F11). The presence of a multiplicative interaction between rs2066865 (FGG) and CAD increased the VTE risk for the Roma population (ß = 0.143, p = 0.046) but not for the general population (ß = -0.329, p < 0.001). Conclusions: rs121909567 (SERPINC1, ATBp3) was confirmed as a founder mutation in the Roma population. Our study revealed some evidence on the burden of the joint presence of genetic and environmental risk factors on VTE, although the finding is highly subjected to the selection and observational biases due to the very small number of VTE cases and the observational nature of the study design, respectively. As a result of higher genetic load and GxE interactions, this minority Roma population is at higher risk of VTE than the general Hungarian population. Thus, our results suggest the need for an intensive search for the rs121909567 (SERPINC1; ATBp3) founder mutation, which might be an important factor for the assessment of thrombotic disease susceptibility among the Roma population. In addition, we strongly recommend further studies among a large number of VTE cases to explore the more precise impact of genetic and environmental risk factors on VTE in the study populations.

Roma Socioeconomic Status Has a Higher Impact on Smoking Behaviour than Genetic Susceptibility.

It is a matter of speculation whether the high prevalence of smoking among Hungarian Roma (HR) is related to genetic, gene-environmental interactions or cultural factors. Our aim is to compare the genetic susceptibility and possible effects of determinants associated with smoking behaviours in the Hungarian general (HG) and Roma populations. A complex health survey including three pillars (questionnaire, physical and laboratory examinations) was carried out (NHG = 412 and NHR = 402). Risk allele frequencies of ten single-nucleotide polymorphisms (SNPs) were compared, and their combined effect was estimated by computing unweighted and weighted genetic risk scores (GRS, wGRS). The effects of genetic and environmental factors were investigated in regression analyses after confounders were introduced. Socio-economic status (SES) was calculated based on the Kuppuswamy scale 2019. Risk allele frequencies of only four SNPs were found to be different between populations (p < 0.01). Median values of GRS did not differ, while the wGRS median was slightly higher among Roma individuals (5.2 vs. 4.9; p = 0.02). Roma individuals were more likely to be heavy smokers (ORmales = 2.05, 95% CI [1.47-2.86]; ORfemales = 1.89, 95% CI [1.58-2.25]. Smokers have lower SES compared to never smokers (SES ßHR = -0.039, p = 0.023; ßHG = -0.010, p = 0.049). An inverse relationship was found between SES and smoking behaviours (p < 0.0001) and was found to be a better predictor of smoking behaviours than genetic susceptibility. Our study findings suggest that the high prevalence of smoking behaviours and nicotine-dependence were not revealed to have a genetic susceptibility among HR individuals; therefore, the highest efforts should be focused on targeting SES-related factors in the Roma population. Strengths of the study: This is the first study carried out to investigate and detect the most relevant factors and the possible genetic background of the extremely high prevalence of smoking based in the Roma population. Limitations of the study: No standard instrument has been used to assess the intensity of addiction to nicotine. Because of some participants' unwillingness to define themselves as Roma, the overall HR population was not represented by the sample of this study.

Epidemiology of Viral Hepatitis from 2007 to 2016 in Karbala Governorate, Iraq.

BACKGROUND: An escalation, as three times more, had been recognized in cases of hepatitis A (HAV) from 2009 to 2014 among Iraqi people. Regarding hepatitis B and C, Iraq is considered as a low endemic country comparing to neighbors. STUDY DESIGN: A retrospective cohort study. METHODS: Data incorporated from 2007 to 2016 were collected through a federal survey conducted by the Health Directorate of Karbala, who administrates all hospitals (three public hospitals and five private hospitals) and 40 health centers in Karbala City, Iraq. The four types of hepatitis and demographic information of all cases were included. RESULTS: A vivid shifting in the prevalence of HAV showed a decreasing pattern, that is, from 632 cases (PR=61) in 2007 to 314 cases (PR=33) in 2008. In 2012, its prevalence was twice greater (695 cases, PR=63.2). The PR of HBV also changed from 52 cases (PR=5.8) in 2007 to 26 cases (PR=2.8) in 2008. Regarding HCV, a decreasing pattern with 13 cases (PR=1.4) in 2007 and 12 cases (PR=1.2) in 2009 was seen. This number increased to 60 cases (PR=3.9) in 2016. For HEV, more cases were reported (47 cases, PR=4.7) in 2010. CONCLUSION: The four types of hepatitis have been highly prevalent since 2010. The high number of migrants to Karbala Governorate and unavailability of immunization might be reasons behind the high prevalence of the four-types of hepatitis.