Search

Vascular endothelial growth factor (VEGF) is a cytokine involved in angiogenesis and upregulated during adaptive heart hypertrophy. Downregulation of VEGF seems to trigger the transition from adaptive to dilated cardiac hypertrophy. We investigated for the first time whether 3 clinically relevant polymorphisms in the VEGFA gene are associated with altered echocardiographic parameters in hypertensive patients. We determined genotypes for 3 polymorphisms in VEGFA promoter in 179 hypertensive patients and 169 healthy controls: g.-2578C>A (rs699947), g.-1154G>A (rs1570360), and g.-634G>C (rs2010963). Although the variant genotypes of the g.-634G>C (GC + CC) were associated with reduced left ventricular mass index (p = 0.030), the variant genotypes for the g.-1154G>A (GA D AA) were associated with reduced ejection fraction (p = 0.008). In addition, we found that VEGFA haplotypes were associated with altered ejection fraction (p = 0.024). The AAG haplotype was associated with reduced ejection fraction (p = 0.010). Our results suggest that VEGF polymorphisms affect cardiac remodeling. Genotypes for VEGFA polymorphisms can be useful to help to identify hypertensive patients at greater intrinsic risk forheart failure. [ABSTRACT FROM AUTHOR]

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis represents one of the most consistent pathophysiological findings in depressive disorders. Cortisol signaling is affected by proteins that mediate its cellular responses or alters its availability to mineralocorticoid and glucocorticoid receptors. In our study, we evaluated candidate genes that may influence the risk for depression and suicide due to its involvement in cortisol signaling. The aim of the study was to assess whether the genotypes of these genes are associated with the risk for depression, severity of depressive symptoms, suicidal ideation, and suicide attempts. And whether there is interaction between genes and early-life stress. In this study, 100 healthy controls and 140 individuals with depression were included. The subjects were clinically assessed using the 21-item GRID-Hamilton questionnaires (GRID-HAMD-21), Beck Scale for Suicidal Ideation (BSI), and the Childhood Trauma Questionnaire (CTQ). A robust multifactorial dimensionality reduction analysis was used to characterize the interactions between the genes HSD11B1 , NR3C1, NR3C2 , and MDR1 and early-life stress. It was found a significant association of the heterozygous genotype of the MDR1 gene rs1128503 polymorphism with reduced risk of at least one suicide attempt (OR: 0.08, p = 0.003*) and a reduction in the number of suicide attempts (β = −0.79, p = 0.006*). Furthermore, it was found that the MDR1 rs1228503 and NR3C2 rs2070951 genes interact with early-life stress resulting in a strong association with depression (p = 0.001). Our findings suggest that polymorphisms in the MDR1 and NR3C2 genes and their interaction with childhood trauma may be important biomarkers for depression and suicidal behaviors. [ABSTRACT FROM AUTHOR]

Lifelong glucocorticoid (GC) replacement is the mainstay treatment of congenital adrenal hyperplasia (CAH) due to classic 21-hydroxylase deficiency (21-OHD). Challenges posed by therapeutic management of these patients are well known, but novel insights into the variability in clinical response to GC highlight a role for single nucleotide polymorphisms (SNPs) of the glucocorticoid receptor gene (NR3C1). To assess whether six commonly studied NR3C1 SNPs, which were previously associated with modified response to GC, are associated with CAH. We further assessed the linkage disequilibrium (LD) among these NR3C1 SNPs and their combination into haplotypes. Genotypes were determined by Taqman allele discrimination assays for Tth111 I (rs10052957), ER22 (rs6189), 23 EK (rs6190), N363S (rs56149945), BclI (rs41423247) and 9β (rs6198) in a Brazilian cohort of 102 unrelated 21-OHD patients and 163 unrelated healthy subjects (controls). Haplotypes were estimated using Haplo.stats, and LD among SNPs using Haploview. Heterozygous subjects for Tth111 I were more frequent in 21-OHD patients (P = 0.004), while heterozygous for BclI were more frequent in controls (P = 0.049). We found a strong LD among the six NR3C1 SNPs, and four out of six common haplotypes contained the Tth111 I - variant. Although we found no significant differences in overall haplotype analysis, the BclI -haplotype was less frequent among 21-OHD patients (P = 0.0180). BclI -haplotype was less common and heterozygous for Tth111 I were more frequent in 21-OHD patients, while heterozygous for BclI were more frequent in controls. Our novel findings may contribute to further clinical studies on the prognostic value of NR3C1 haplotypes towards individualized treatment for 21-OHD patients. • Glucocorticoid replacement in patients with congenital adrenal hyperplasia is a challenge. • NR3C1 polymorphisms play a role on variable clinical response to glucocorticoids. • Heterozygous- Tht111 I was more frequent in cases with congenital adrenal hyperplasia. • Heterozygous- BclI was more frequent in healthy subjects from the control group. • The BclI -haplotype was less frequent in cases with congenital adrenal hyperplasia. [ABSTRACT FROM AUTHOR]

• miRNA expression between cardiotoxicity and non-cardiotoxicity breast cancer patients. • Let-7f, miR-1, miR-20a, miR-126 and miR-210 may predict anthracycline-induced cardiotoxicity in breast cancer patients. • Target genes from miRTarBase for these five miRNAs uncovered relevant Reactome pathways. Cardiotoxicity is a common and serious adverse effect of anthracycline therapy in breast cancer patients. The current criteria for cardiotoxicity are based on imaging and cardiac biomarkers. However, there is a need for new biomarkers to help with early diagnosis. MicroRNAs (miRNAs) are small non-coding RNA molecules that play an important role in the regulation of gene expression. Several miRNAs have been associated with cardiovascular diseases and are biomarkers under investigation for cancer treatment-related cardiotoxicity. We performed a systematic literature search of Medline/PubMed, Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Web of Science and Embase, until April 2020. Cohort studies that reported miRNA biomarkers in breast cancer patients with anthracycline-induced cardiotoxicity and non-cardiotoxicity patients were included. Moreover, we searched the miRTarBase for experimentally validated miRNA-target interactions. Among the 209 studies retrieved, five fulfilled the inclusion criteria. Let-7f, miR-1, miR-20a, miR-126 and miR-210 were validated in two population-based cohorts. The pro-angiogenic miRNAs let-7f, miR-20a, miR-126 and miR-210 were significantly down-regulated in epirubicin-cardiotoxicity when compared to the non-cardiotoxicity group. miR-1 has been shown to provide diagnostic and prognostic information in the setting of myocardial infarction, but changes in its levels are controversial in doxorubicin-treated breast cancer patients with cardiotoxicity. Reactome pathways relevant to cardiotoxicity were found from the target genes for let-7f, miR-1, miR-20a, miR-126 and miR-210 at miRTarBase. The data suggest that let-7f, miR-1, miR-20a, miR-126 and miR-210 are associated with anthracycline-based cardiotoxicity during chemotherapy in breast cancer patients. [ABSTRACT FROM AUTHOR]