Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 x10(-8)), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

COVID-19 in Children with Congenital Heart Diseases: A Multicenter Case Series from Iran

Background. Promptly discovering and counteracting COVID-19 is critical as it could have catastrophic effects. As an asymptomatic group, children are highly susceptible to be misdiagnosed, especially those suffering from underlying diseases. Furthermore, discriminating the direct effects of the virus from those of the underlying diseases can pose a dilemma to physicians. This case series aims to determine the relationship between COVID-19 and various types of congenial heart disease among children. Patients and Methods. Seven patients from three different medical centers were enrolled. Their detailed demographic information, past medical history, symptoms, type of congenital heart diseases, imaging tests, laboratory tests, medications, and outcomes were analyzed. Results. The patients included 4 infants, 1 child, and 2 adolescents, with a median age of 9 months and a majority of boys. All of them had either obstructive lesions (right or left ventricular outflow tracts) or significant pulmonary hypertension. The more common clinical symptoms were cough, dyspnea, and fever. Two patients did not survive the illness. Conclusion. Prompt treatment of patients with a combination of COVID-19 and severe obstructive cardiac pathology or pulmonary hypertension is essential due to a risk for serious and/or fatal consequences

The level of urinary endothelin in patients with urinary reflux

Background: In different tissues, the endothelin is produced by vascular endothelium. They are potent vasoconstrictor peptides. There is a little information about the role of endothelin in reflux nephropathy. Objectives: The aim of this study is to evaluate urinary levels of endothelin in patients with vesicoureteral reflux (VUR). Patients and Methods: It was a cross-sectional study that conducted on 81 children who received voiding cystourethrogram (VCUG). Based on VCUG reports, patients were divided into two groups; with reflux (40 persons) and without reflux (41 persons). We got a urine sample from patients with mid-stream or urine bag method. The endothelin level was assessed with ELISA immunoassay. Data was analyzed using SPSS 16. Results: Based on VCUG reports, 40 patients (49.4%) had urinary reflux, of them 20 cases suffered from unilateral urinary reflux and others from bilateral. Of 40 patients with reflux, 23 cases (57.5% of reflux group) had kidney scar and seven individuals (17.5%) had abnormal kidney sonography. Of patients with urinary reflux, 13 cases (32.5%) had grade1 urinary reflux, 8 cases (20%) grade 2, and 5 cases (12.5%) grade 3 and finally 14 cases (35%) grade 4. The UET-1 levels were significantly higher in VUR patients compared to the control group (P < 0.001). Comparison of mean endothelin levels between two groups was done using Mann-Whitney U test and was statistically significance (P < 0.001). We used Kruskal-Wallis for comparison of endothelin levels in different grades of reflux (P < 0.001). Conclusions: Urine endothelin-1 level can be considered as an alternative to VCUG for screening vesicourethral reflux

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10-8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Abstract Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P &lt;5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate&lt;0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD