Comparing vitamin D receptor gene polymorphisms in rs11568820, rs7970314, rs4334089 between COVID-19 patients with mild and severe symptoms: a case control study.

The associations of vitamin D receptor (VDR)- single nucleotide polymorphisms (SNPs) with the symptoms of COVID-19 may vary between patients with different severities of COVID-19. Therefore, in the present study, we aim to compare VDR polymorphisms in severe and mild COVID-19 patients. In this study, a total number of 85 hospitalized patients and 91 mild/moderate patients with COVID-19 were recruited. SNPs in VDR genes were determined using ARMS and then confirmed by sanger sequencing. The mean (SD) age of participants in hospitalized and non-hospitalized group was 59.0 (12.4) and 47.8 (14.8) years, respectively. Almost 46% of participants in hospitalized and 48% of participant in non-hospitalized group were male. The frequency of TT genotype of SNP rs11568820 was significantly lower in hospitalized than non-hospitalized group (3.5% vs. 17.6%; P = 0.018). However, there was no significant differences between genotypes of SNPs rs7970314 and rs4334089 and also alleles frequencies in all SNPs of two groups. The genotype of rs11568820 SNP had an inverse association with hospitalization of patients with COVID-19 after adjustment for comorbidities [OR 0.18, 95% CI 0.04, 0.88; P = 0.034]. While, there was no relationship between genotypes of SNPs rs7970314 and rs4334089 and hospitalization. The TT genotype of rs11568820 plays protective role in sever COVID-19 and hospitalization. Further studies with a large sample size which consider various confounding factors are warranted to confirm our results.

Genetic variation in salt taste receptors impact salt intake and blood pressure.

So far, few studies have examined the effect of salt taste receptors genetic variation on dietary intake in the Iranian population. We aimed to evaluate associations between single nucleotide polymorphisms (SNPs) in salt taste receptors' genes with dietary salt intake and blood pressure. A cross-sectional study was carried out among 116 randomly selected healthy adults aged ≥ 18 in Isfahan, Iran. Participants underwent sodium intake determination by 24-h urine collection, as well as dietary assessment by semi-quantitative food frequency questionnaire and blood pressure measurement. Whole blood was collected to extract DNA and genotype of SNP rs239345 in SCNN1B and rs224534, rs4790151 and rs8065080 in TRPV1 gene. Sodium consumption and diastolic blood pressure were significantly higher in carriers of the A-allele in rs239345 compared to subjects with the TT genotype (4808.4 ± 824.4 mg/day vs. 4043.5 ± 989.3 mg/day; P = 0.004) and 83.6 ± 8.5 mmHg vs. 77.3 ± 7.3 mmHg; P = 0.011), respectively. The level of sodium intake was lower in the TT genotype of TRPV1 (rs224534) than the CC genotype (3767.0 ± 713.7 mg/day vs. 4633.3 ± 793.5 mg/day; P = 0.012). We could not find any association between genotypes of all SNPs with systolic blood pressure as well as genotypes of rs224534, rs4790151 and rs8065080 with diastolic blood pressure. Genetic variations can relate with salt intake and consequently may associate with hypertension and finally cardiovascular disease risk in the Iranian population.

Association study of polymorphism in Thrombomodulin gene [rs1042579] with cardiovascular disease.

BACKGROUND AND AIM: Thrombomodulin (THBD) gene plays an important role in activation and control of protein C. Regulation protein C levels as an important risk factor for cardiovascular disease. Mutations in this gene can affect Thrombomodulin levels. In this study, we aimed to investigate the role of single nucleotide polymorphism (SNP) in rs1042579 THBD gene in patients with cardiovascular disease. METHODS: The samples of this case-control study consisted of 105 Iranian patients with cardiovascular disease and 95 healthy controls who enrolled from March 2017 to December 2018 in this study.  Demographic data, medical history, and para-clinical were measured, and Sanger sequencing was used for allelic discrimination. Control samples were identified and then selected for genotyping of other ARMS-PCR technique. RESULTS: Data analysis revealed that the rs1042579 polymorphism of the THBD gene was associated with a risk of coronary heart disease. Sequencing results confirmed the existence of CC homozygous, heterozygous TC and TT homozygous genotypes. TT genotype is a risk factor in patients compared to healthy controls. CONCLUSION: The results of this study showed that the rs1042579 polymorphism was associated with an increased risk of cardiovascular disease.

Risk Factors for In-Hospital Mortality among Patients with Coronavirus-19 in Isfahan City, Iran.

Background: The aim of the study is to explore the risk factors of mortality for hospitalized patients in three designated hospitals in Isfahan province. Materials and Methods: This retrospective cohort study was conducted on all positive coronavirus disease (COVID)-19 patients admitted to Khorshid, Isabn Maryam, and Amin hospitals in Isfahan province. The demographic, clinical, laboratory, and outcome data of patients who were died or discharged from February 24, 2020, to April 18, 2020, were extracted from patient's medical records. Results: Overall 1044 COVID-19 patients were included in this analysis. Based on the findings of this study, older age (≥65 years) (adjusted hazard ratio [aHR]: 2.06; 95% confidence interval [CI]: 1.13-3.76), chronic obstructive pulmonary disease (COPD) history (aHR: 2.52; 95% CI: 1.09-5.83), white blood cell (WBC) counts more than 10 × 10^3/L (aHR: 3.05; 95% CI: 1.42-6.55), Hb level <13 gr/L (aHR: 2.82; 95% CI: 1.34-5.93), bilateral pulmonary infiltrates (aHR: 2.02; 95% CI: 1.12-3.64) at admission, development of acute respiratory distress syndrome (ARDS) (aHR: 1.87; 95% CI: 1.01-3.47), and intensive care unit (ICU) admission (aHR: 2.09; 95% CI: 1.04-4.18) during hospitalization were risk factors for in-hospital mortality in patients with COVID-19. Conclusions: Multiple factors were found related to the severity and death among COVID-19 patients. We were found that older age (≥65 years) with COPD history, high level of WBC, low level of Hb (<13 g/L), bilateral pulmonary infiltrates at admission, development of ARDS, and ICU admission during hospitalization were identified as risk factors of death among COVID-19 patients. More related studies are needed in the future.

Precision medicine and metabolic syndrome.

Metabolic syndrome (MetS) is one of the most important health issues around the world and a major risk factor for both type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The etiology of MetS is determined by the interaction between genetic and environmental factors. Effective prevention and treatment of MetS notably decreases the risk of its complications such as diabetes, obesity, hypertension, and dyslipidemia. According to recent genome-wide association studies, multiple genes are involved in the incidence and development of MetS. The presence of particular genes which are responsible for obesity and lipid metabolism, affecting insulin sensitivity and blood pressure, as well as genes associated with inflammation, can increase the risk of MetS. These molecular markers, together with clinical data and findings from proteomic, metabolomic, pharmacokinetic, and other methods, would clarify the etiology and pathophysiology of MetS and facilitate the development of personalized approaches to the management of MetS. The application of personalized medicinebased on susceptibility identified genomes would help physicians recommend healthier lifestyles and prescribe medications to improve various aspects of health in patients with MetS. In recent years, personalized medicine by genetic testing has helped physicians determine genetic predisposition to MetS, prevent the disease by behavioral, lifestyle-related, or therapeutic interventions, and detect, diagnose, treat, and manage the disease. Clinically, personalized medicine is providing effective strategies for the prevention and treatment of MetS by reducing the time, cost, and failure rate of pharmaceutical clinical trials. It is also eliminating trial-and-error inefficiencies that inflate health care costs and undermine patient care.

Apolipoprotein B gene mutation related to familial hypercholesterolemia in an Iranian population: With or without hypothyroidism.

BACKGROUND: Familial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol (LDL-C) levels in plasma. Mutations of its related gene; apolipoprotein B (APOB) is seen in about two percent of the patient with FH. Thyroid disease is usually part of the exclusion criteria for the detection of FH which alters the lipid profile. We evaluated mutations in the APOB gene in patients with high LDL-C levels. MATERIALS AND METHODS: Patients aged between 2 and 80 years with at least one LDL-C level of more than 190 mg/dl were selected (120 patients) from Isfahan Laboratories. Blood samples were obtained from all patients. Genomic DNA was extracted. Primer sequences were designed by Oligo 7.60 to amplify the desired 844 bp region of exon 26 of the APOB gene containing R3500Q and R3500W variants associated with FH. RESULTS: Overall, two patients showed a heterozygous form of a common pathogenic variant in exon 26 named c. 10579 C > T (R3500W, cDNA.10707), and one patient was hypothyroidism. We also recognized another nonpathognomonic variant c. 10913G > A (rs1801701, cDNA.11041) in 13 patients, two of them were hypothyroidism. CONCLUSION: This study for the first time shows the coexistence of APOB mutation in hypothyroidism, which emphasis screening of patients with hypothyroid for FH detection.

Morning Exercise at School and Sedentary Activities are Important Determinants for Hypertension in Adolescents.

BACKGROUND: This study was performed to determine the association of Pre-hypertension/hypertension (pre-HTN/HTN) with leisure-time activities and morning exercise at school in a sample of Iranian adolescents. METHODS: This secondary study has done using data of 1992 adolescents participated in of Isfahan Healthy Heart Program. The outcome variable was having/not having pre-hypertension/hypertension (pre-HTN/HTN). The students with Blood pressure (BP) between 90th to 95th percentiles were considered as positive pre-HTN and students with BP >95th percentile were considered as positive HTN. Students with pre-HTN or HTN were considered as positive pre-HTN/HTN. The asked leisure-time activities were categorized in three group including first (ping-pong, basketball, and volleyball), second (football, walking, and bicycling) and sedentary activities (watching TV, studying, and computer gaming), using factor analysis. RESULTS: The prevalence of pre-HTN and HTN was 16.1% and 6.7%, respectively. Based on multiple logistic regression pre-HTN/HTN was associated just with sedentary activities and morning exercise at school. Odds Ratio (95% confidence interval) for sedentary activities and morning exercise at school was 1.51 (1.13-2.01) and 0.63 (0.44-0.89), respectively. CONCLUSION: We observed adolescents who engaged in morning exercise at school had lower prevalence of HTN while those who spent more times on sedentary activities were in higher risk for HTN. We suggest to permanent holding of morning exercise and educational programs on healthy lifestyle skills for adolescents by schools.

How Are Epigenetic Modifications Related to Cardiovascular Disease in Older Adults?

The rate of aging has increased globally during recent decades and has led to a rising burden of age-related diseases such as cardiovascular disease (CVD). At the molecular level, epigenetic modifications have been shown recently to alter gene expression during the life course and impair cellular function. In this regard, several CVD risk factors, such as lifestyle and environmental factors, have emerged as key factors in epigenetic modifications within the cardiovascular system. In this study, we attempted to summarized recent evidence related to epigenetic modification, inflammation response, and CVD in older adults as well as the effect of lifestyle modification as a preventive strategy in this age group. Recent evidence showed that lifestyle and environmental factors may affect epigenetic mechanisms, such as DNA methylation, histone acetylation, and miRNA expression. Several substances or nutrients such as selenium, magnesium, curcumin, and caffeine (present in coffee and some teas) could regulate epigenetics. Similarly, physical inactivity, alcohol consumption, air pollutants, psychological stress, and shift working are well-known modifiers of epigenetic patterns. Understanding the exact ways that lifestyle and environmental factors could affect the expression of genes could help to influence the time of incidence and severity of aging-associated diseases. This review highlighted that a healthy lifestyle throughout the life course, such as a healthy diet rich in fibers, vitamins, and essential elements, and specific fatty acids, adequate physical activity and sleep, smoking cessation, and stress control, could be useful tools in preventing epigenetic changes that lead to impaired cardiovascular function.

Effects of selenium intake on the expression of prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2) and matrix metallopeptidase-9 genes in the coronary artery disease: Selenegene study, a double-blind randomized controlled trial.

BACKGROUND: The oxidative stress is regarded as one of the main contributors to the health problem. Cyclooxygenase-2 (COX-2) and matrix metallopeptidase-9 (MMP-9) are two of the important genes that are reported to be involved in the cardiovascular disease (CVD) development in the molecular and genetic association studies. The aim of this study was to evaluate the level of expression of COX-2 and MMP-9 after selenium supplementation in patients with coronary artery disease (CAD). METHODS: In this sub-study of Selenegene study, subjects were randomly divided into groups, 19 subjects who received selenium and 22 patients with CAD who received placebo. Patients received either 200-mg selenium yeast tablets or placebo tablets after a meal, once daily for 60 days. The messenger ribonucleic acid (mRNA) levels of the selenium and prostaglandin-endoperoxide synthase 2 (PTGS2) (COX-2) and MMP-9 genes products were determined before and after the study. RESULTS: In this sub-study, 41 Iranian patients with CVD were enrolled (placebo group: n = 22, selenium intervention: n = 19). Fasting blood sugar (FBS) was higher among placebo group than selenium group (93.4 ± 12.7 vs. 124.4 ± 40.6 mg/dl, P = 0.03). Triglyceride (TG) level was higher among selenium group versus placebo group (123.3 ± 34.0 vs. 184.8 ± 69.4 mg/dl, P = 0.006). The data analysis demonstrated that the expression of MMP-9 and COX-2 genes did not change significantly in both selenium and placebo groups. CONCLUSION: This study showed a positive association between the expression of MMP-9 and COX-2 in the patients with CAD who received selenium but not the placebo groups. Yet, these findings need to be confirmed in further details and expanded sample size.

Development and validation of a socioeconomic status short-form questionnaire (SES-SQ).

BACKGROUND: Evaluation of socioeconomic status (SES) is an important aspect in community-based health studies and it is a major predictor of health and nutritional status as well as mortality and morbidity from many diseases. This study aimed to construct and validate socioeconomic status short-from questionnaire (SES-SQ) in Iranian population. METHODS: This cross-sectional methodological study was conducted among 1437 Iranian general population. Face and content validity of the developed questionnaire was evaluated qualitatively. Internal consistency, construct validity using exploratory factor analysis (EFA) and latent class analysis (LCA), and convergent and known-group validity were also evaluated. RESULTS: The SES-SQ consisted of 6 items. The overall Cronbach's alpha was 0.64, showing acceptable internal consistency. EFA resulted in two factors explaining 47.78% of total variance. Three SES classes (low/middle/high) were extracted by LCA. The score of SES-SQ ranged from 0 to 17; two cutoff scores of 4.5 and 8.5 were determined by receiver operating characteristic (ROC) analysis for differentiating low from middle and middle from high SES classes, respectively. CONCLUSION: An efficient, reliable, and valid short-form questionnaire was developed for evaluating SES in Iranian general population. The relevancy of questionnaire items is not lost over time.

Polymorphisms of LPA gene, rs1801693 and rs7765781, are not associated with premature myocardial infarction in the Iranian population.

BACKGROUND: Myocardial infarction (MI) is one of the leading causes of mortality globally. Although it is most prevalent in the elderly, it may occur in young adults (men ≤ 55 years or women ≤ 65 years) as premature MI (PMI). As awareness of genetic risks may lead to effective prevention of PMI, we aim to investigate the association of two susceptible single nucleotide polymorphisms (SNPs) in the LPA gene with PMI in the Iranian population, rs1801693 and rs7765781, identified in previous genome-wide association studies (GWAS). METHODS: A total number of 85 patients with PMI and 85 healthy controls were recruited from December 2015 to March 2016 from Isfahan, Iran. Peripheral blood samples were collected from all individuals. Deoxyribonucleic acid (DNA) was extracted and genotyped at rs1181693 and rs7765781 polymorphisms, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results were statistically analyzed to find any possible association of the two polymorphisms with PMI by SPSS software and P-values less than 0.05 were considered to be statistically significant. RESULTS: Statistical analysis displayed no significant difference between rs1801693 (P = 0.815)/rs7765781 (P = 0.746) alleles in patients with PMI and healthy control subjects. CONCLUSION: There is no meaningful association between rs1801693/rs7765781 and PMI incidence in the Iranian population.

The incidence and outcome of severe hyperlactatemia in critically ill patients.

This study aimed to assess the incidence, persistence, and associated mortality of severe hyperlactatemia in a large cohort of unselected critically ill patients. Also, we evaluated the association between 12 h lactate clearance, the timing of severe hyperlactatemia, and the maximum lactate levels with ICU mortality. In this retrospective, single-center study, we used data from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database. Data extracted to screen 23,598 ICU patients for severe hyperlactatemia. A total of 23,598 critically ill patients were eligible for this study. Overall, ICU mortality in the 23,598 ICU patients was 12.1%. Of these, 760 patients had lactate concentration [Formula: see text] 10 mmol/L and ICU mortality in this group was 65%. Our findings confirm the association between hyperlactatemia and ICU mortality [odds ratio 1.42 (95% CI 1.35; 1.49; P < 0.001)]. Data for 12 h lactate clearance was available for 443 patients (276 nonsurvivable vs. 167 survival). 12 h lactate clearance yielded a high area under the curve (AUC) of 0.78, (95% CI 0.74 and 0.83). Severe hyperlactatemia is associated with extremely high ICU mortality in a heterogeneous ICU population. Lactate derived variables (the timing and persistence of severe hyperlactatemia, maximum level, and 12 h clearance) are shown to be associated with ICU mortality in patients with severe hyperlactatemia. Our results suggest that maximum lactate level and 12 h lactate clearance were clinically useful prognostic parameters for patients with severe hyperlactatemia.

Lactate/albumin ratio: An early prognostic marker in critically ill patients.

OBJECTIVES: We investigate the clinical utility of the lactate/albumin (L/A) ratio as an early prognostic marker of ICU mortality in a large cohort of unselected critically ill patients. METHODS: A retrospective single-center study using data from the Multiparameter Intelligent Monitoring Intensive Care III (MIMIC-III) database collected between 2001 and 2012. We screened adult patients (age ≥ 15) with measured lactate and albumin on the first day of ICU stay to evaluate the prognostic performance of the lactate and lactate/albumin (L/A) ratio for ICU mortality prediction. RESULTS: The overall ICU mortality in the 6414 eligible ICU patients was 16.4%. L/A showed a receiver-operating characteristics area under the curve (ROC-AUC) value of 0.69 (95% CI: 0.67, 0.70) to predict ICU mortality, higher than lactate 0.67 (95%CI: 0.65, 0.69). Regardless of the lactate level, L/A yielded better ROC-AUC compared to the lactate level [normal lactate (<2.0 mmol/L): 0.63 vs 0.60; intermediate lactate (2.0 mmol/L ≤ lactate <4.0 mmol/L): 0.58 vs 0.56; high lactate (≥4.0 mmol/L): 0.67 vs 0.66]. L/A was a better prognostic marker for ICU mortality in patients with decreased lactate elimination [hepatic dysfunction: 0.72 vs 0.70; renal dysfunction 0.70 vs 0.68]. The L/A ratio ROC-AUC was better in patients with sepsis (0.68 vs 0.66) and those who developed severe sepsis or septic shock (0.68 vs 0.66). CONCLUSIONS: The performance of L/A and lactate were equivalent in predicting ICU mortality and can be used as early prognostic markers for ICU patients with different initial lactate level and the presence of hepatic or renal dysfunction.

The Epigenetic Overlap between Obesity and Mood Disorders: A Systematic Review.

(1) Background: Obesity and mood disorders are considered as the most prevalent morbidities in many countries. We suppose that epigenetic mechanisms may induce higher rates of obesity in subjects who suffer from mood disorders. In this systematic review, we focused on the potential roles of DNA methylation on mood disorders and obesity development. (2) Methods: This systematic review was conducted in accordance with the PRISMA statement and registered in Prospero. A systematic search was conducted in MEDLINE, Scopus, Web of Science, Cochrane Central database, EMBASE, and CINHAL. We also conducted a Grey literature search, such as Google Scholar. (3) Results: After deduplication, we identified 198 potentially related citations. Finally, ten unique studies met our inclusion criteria. We have found three overlap genes that show significant DNA methylation changes, both in obesity and depression. Pathway analysis interaction for TAPBP, BDNF, and SORBS2 confirmed the relation of these genes in both obesity and mood disorders. (4) Conclusions: While mechanisms linking both obesity and mood disorders to epigenetic response are still unknown, we have already known chronic inflammation induces a novel epigenetic program. As the results of gene enrichment, pathways analysis showed that TAPBP, BDNF, and SORBS2 linked together by inflammatory pathways. Hypermethylation in these genes might play a crucial rule in the co-occurrence of obesity and mood disorders.

Risk factors of congenital heart diseases: A hospital-based case-control study in Isfahan, Iran.

BACKGROUND: Improving knowledge towards risk factors for congenital heart disease (CHD) is important because of its high mortality and morbidity and trying for prevention of occurrence of CHD. METHODS: This case-control study was conducted on a total of 898 children with their mothers, who referred to the Clinic of Pediatric Cardiology of School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran, during the years of 2014 to 2016. Cases comprised of 464 children with CHD diagnosed by echocardiography and controls were 434 sex- and age-matched children without any evidence of CHD, who were admitted for a heart check-up at the same study period and in similar conditions. The children's parents completed check lists for collecting demographic characteristics, family history of CHD, history of obesity in mother, history of abortion and diseases in mother, use of medicine during pregnancy, exposure to teratogens during pregnancy, and children characteristics such as birth height and birth weight, etc. RESULTS: Based on the results of data analyses with multiple logistic regression model [odds ratio (OR) with 95% confidence interval (CI)], history of obesity in mother before pregnancy, history of abortion, parental consanguinity, exposure to cigarette smoke during pregnancy, exposures to teratogens in the first trimester of the pregnancy, and use of medicine during pregnancy were associated with an increased odds of CHDs. CONCLUSION: Results of this study emphasizes the use of policies that enhance pre-marital counseling, regular counseling during pregnancy, treatment of mothers' disease, and enhancing knowledge of women of childbearing age about exposure to certain teratogens for controlling risk factors of CHD.

Association of Selenoprotein S Expression and its Variants with Metabolic Syndrome in Subjects with Cardiovascular Disease.

BACKGROUND: Selenoproteins S (SELS or VIMP) may regulate cytokine production, and thus play a key role in the control of the inflammatory response. METHODS: This study consisted of 136 Iranian patients with cardiovascular disease (65 MetS-affected and 71 MetS un-affected individuals) in the selengene study. Expression of two variants of VIMP including VIMP I and II were analyzed in all subjects using Real-Time PCR and ELISA. RESULTS: The level of VIMP was lower in MetS+ compared to the MetS- subjects (p <0.05). We found no significant differences in quantitative expression of VIMP I and VIMP II in both groups. VIMP I reveal a reverse correlation with fasting blood sugar (FBS) (r = -0.45, p = 0.009). Moreover, SELS in protein level has negative correlation with WC (r = -0.171, p = 0.049) and positive correlation with HDL (r = 0.176, p = 0.046). CONCLUSIONS: Our study suggests that VIMP in protein level is significantly lower in MetS and shows a reverse correlation with WC and positive correlation with HDL. Therefore, with regard to the functional role of this protein, it is possible to deduce that its lower expression leads to the higher secretion of unfolded proteins into the cytosol and outside the cell, where they cannot play their exact roles in the different pathways. Moreover, the reverse correlation of VIMP I with FBS suggests further consideration of VIMP and its variant VIMP I expression in regards to potential development of major CVD risk factors.

Depression screening using mobile phone usage metadata: a machine learning approach.

OBJECTIVE: Depression is currently the second most significant contributor to non-fatal disease burdens globally. While it is treatable, depression remains undiagnosed in many cases. As mobile phones have now become an integral part of daily life, this study examines the possibility of screening for depressive symptoms continuously based on patients' mobile usage patterns. MATERIALS AND METHODS: 412 research participants reported a range of their mobile usage statistics. Beck Depression Inventory-2nd ed (BDI-II) was used to measure the severity of depression among participants. A wide array of machine learning classification algorithms was trained to detect participants with depression symptoms (ie, BDI-II score ≥ 14). The relative importance of individual variables was additionally quantified. RESULTS: Participants with depression were found to have fewer saved contacts on their devices, spend more time on their mobile devices to make and receive fewer and shorter calls, and send more text messages than participants without depression. The best model was a random forest classifier, which had an out-of-sample balanced accuracy of 0.768. The balanced accuracy increased to 0.811 when participants' age and gender were included. DISCUSSIONS/CONCLUSION: The significant predictive power of mobile usage attributes implies that, by collecting mobile usage statistics, mental health mobile applications can continuously screen for depressive symptoms for initial diagnosis or for monitoring the progress of ongoing treatments. Moreover, the input variables used in this study were aggregated mobile usage metadata attributes, which has low privacy sensitivity making it more likely for patients to grant required application permissions.

Determining genetic variants in children and adolescents suffering from tetralogy of Fallot with a positive family history: methodology.

BACKGROUND AND AIM: Congenital heart disease (CHD) affects near 1% of all live births and is considered to be the main reason of morbidity and mortality in early childhood. In this study, we investigated molecular genetics factors associated with Tetralogy of Fallot (TOF) using high throughput technologies in the consanguineous families with at least 2 affected individual. METHOD: This family study started in March 2017 to May 2018 in pediatric cardiovascular research center, Cardiovascular Research Institute, Isfahan, Iran. After obtaining informed consent, we invited families who had at least 2 individuals in one generation or previous generations with familial marriage history and they were included in the study. Genomic DNA was extracted from peripheral blood lymphocytes of the patient and samples were investigated for structural variations such as deletion or duplication in the genome using single nucleotide polymorphism array (SNP array). In the next step, if the SNP array is negative, next generation study will be performed in the propend and after analyzing the raw data and filtering for rare pathogenic variants. RESULTS: In this study, totally 5 families were evaluated. All affected and unaffected individuals of each family included in the pedigree.  This study comprised 14 subjects (9 males and 5 females; 8.92 ± 6.21 years old). Baseline characteristics and clinical data of the study subjects are presented in Table 1. The prevalence of consanguineous marriage is 92.2% among parents, 71.4% among mother grandparents and 28.6% among father grandparents. 64.3 % of our participants have sibling with similar disease. The prevalence of atrial septal defect (ASD), ventricular septal defect (VSD), and arrhythmia and TOF was 7.1%. CONCLUSION: We found some families with 2 or more CHD and with a high rate of consanguineous marriage and probably suffering from a genetic predisposition. We aim to exam them further with next generation study (NGS) to find any genetic defect and then to exam other CHD's in our region. Key words: gene mutations, children, adolescents, tetralogy of Fallot, family history.

Effect of single nucleotide polymorphisms in SEPS1 and SEPP1 on expression in the protein level in metabolic syndrome in subjects with cardiovascular disease.

Metabolic syndrome (MetS) results from the interaction between environmental and genetic factors. Several previous studies considered the role of selenium in developing MetS. Two selenoproteins, selenoprotein S (SelS), and the Selenoprotein P (SePP) play an important role in antioxidative defense and therefore susceptibility to MetS. The involvement of SNPs in SEPP1 and SEPS1 have not been studied in MetS subjects. This study aims to investigate the association between the risk of MetS and four polymorphisms SEPS1 (rs28665122, rs4965373), SEPP1 (rs7579, rs3877899) in an Iranian population. The sample of this case-control study consisted of 132 Iranian patients with cardiovascular disease (71 MetS and 65 non-MetS subjects) from December 2015 to March 2016. Demographic data, medical history, and para-clinical were measured, and Taqman probes were used for allelic discrimination. The level of the SelS and the SePP were measured by the ELIZA method. No significant differences were found in the genotype frequencies of SEPS1 (rs4965373, rs28665122), SEPP1 (rs7579, rs3877899) in patients with MetS and the non-MetS group. The mean of SelS in MetS subjects with SEPS1 (rs4965373) GG genotype is significantly lower than the non-MetS group (4496.99 ± 3688.5 vs. 6148.6 ± 1127.0, P = 0.009). The mean of SePP in MetS subjects with SEPP1 (rs3877899) GG genotype is significantly lower than the non-MetS group (40.73 ± 8.44 vs.83.91 ± 21.33, P = 0.002). The mean of SePP in MetS subjects with SEPP1 (rs7579) GG genotype is lower than the non-MetS group (55.52 ± 16.7 vs. 109.48 ± 29.78, P = 0.01). In summary, the results of this study does not indicate significant differences in the SEPP1 (rs7579, rs3877899) and SEPS1 (rs4965373, rs28665122) genotypes between MetS and non-MetS subjects. However, the results show that the mean of expression of SelS and SePP decreased in the subjects with SEPP1 (rs7579) GG and SEPP1 (rs3877899) GG.