Südame müksoom

Südame müksoom (SM) on kõige sagedasem südame primaarne tuumor. Kuigi histoloogiliselt healoomuline, võib ta oma asukohast tingituna tuua kaasa tõsiseid hemodünaamilisi ja embolitest põhjustatud tagajärgi ning raskematel juhtudel äkksurma. SMi harva esinemise tõttu diagnoos sageli hilineb, sest haigus võib kulgeda asümptomaatiliselt või mittespetsiifilise kliinilise pildiga. Enamasti diagnoositakse SM juhuleiuna või alles embooliliste tüsistuste ilmnemisel. SMi diagnoosimisel on kuldseks standardiks ehhokardiograafia ning ainukeseks tõhusaks ravimeetodiks on tuumori kirurgiline eemaldamine. Patsientide pikaajaline prognoos on kirurgilise ravi järel hea ning sporaadiliste müksoomide retsidiveerumise tõenäosus väike.Artiklis on antud ülevaade südame müksoomi olemusest, epidemioloogiast, kliinilisest pildist, diagnoosimisest, ravist ja prognoosist

Kaasasündinud südamerikete interdistsiplinaarne käsitlus Eestis

Kaasasündinud südamerikked on juba sündides esinevad südame ja suurte veresoonte ehituslikud vead ning need on sagedasimad väärarendid elusalt sündinud lastel. Kaasasündinud südamerikete esinemissagedus on keskmiselt 7–10 juhtu 1000 elussünni kohta aastas (1). Seega sünnib igal aastal Eestis hinnanguliselt 95–120 südamerikkega last. Erinevaid südamerikkeid esineb erineva sagedusega. Sagedasemad kolm neist – vatsakeste vaheseina defekt, kodade vaheseina defekt ja avatud arterioosjuha – moodustavad ligi 60% kõikidest südameriketest (1), kuid lisaks neile ja teistele harvemini esinevatele südameriketele teevad just erinevad rikete kombinatsioonid selle patsiendipopulatsiooni äärmiselt heterogeenseks. Artiklis on antud lühiülevaade kaasasündinud südamerikete põhjustest, diagnostikast, tänapäevasest ravikäsitlusest ning probleemidest

Correction to: Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits

Erratum for Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits. [BMC Med Genomics. 2019

Variation in the SERPINA6SERPINA1 locusalters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expressionin peripheral tissues, and risk of cardiovascular disease

The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variation

Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease

The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from similar to 2.2 M to similar to 7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and alpha 1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06-0.59) and myocardial infarction (0.21, 95% CI 0.00-0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.</p

Global analysis of A-to-I RNA editing reveals association with common disease variants

RNA editing modifies transcripts and may alter their regulation or function. In humans, the most common modification is adenosine to inosine (A-to-I). We examined the global characteristics of RNA editing in 4,301 human tissue samples. More than 1.6 million A-to-I edits were identified in 62% of all protein-coding transcripts. mRNA recoding was extremely rare; only 11 novel recoding sites were uncovered. Thirty single nucleotide polymorphisms from genome-wide association studies were associated with RNA editing; one that influences type 2 diabetes (rs2028299) was associated with editing in ARPIN. Twenty-five genes, including LRP11 and PLIN5, had editing sites that were associated with plasma lipid levels. Our findings provide new insights into the genetic regulation of RNA editing and establish a rich catalogue for further exploration of this process

Opportunities and challenges for transcriptome-wide association studies

Transcriptome-wide association studies (TWAS) integrate genome-wide association studies (GWAS) and gene expression datasets to identify gene-trait associations. In this Perspective, we explore properties of TWAS as a potential approach to prioritize causal genes at GWAS loci, by using simulations and case studies of literature-curated candidate causal genes for schizophrenia, low-density-lipoprotein cholesterol and Crohn's disease. We explore risk loci where TWAS accurately prioritizes the likely causal gene as well as loci where TWAS prioritizes multiple genes, some likely to be non-causal, owing to sharing of expression quantitative trait loci (eQTL). TWAS is especially prone to spurious prioritization with expression data from non-trait-related tissues or cell types, owing to substantial cross-cell-type variation in expression levels and eQTL strengths. Nonetheless, TWAS prioritizes candidate causal genes more accurately than simple baselines. We suggest best practices for causal-gene prioritization with TWAS and discuss future opportunities for improvement. Our results showcase the strengths and limitations of using eQTL datasets to determine causal genes at GWAS loci

European Society of Cardiology Working Group on Adult Congenital Heart Disease and Study Group for Adult Congenital Heart Care in Central and South Eastern European Countries consensus paper : current status, provision gaps and investment required

Aims: To examine the current status of care and needs of adult congenital heart disease (ACHD) services in the Central and South Eastern European (CESEE) region. Methods and results: We obtained data regarding the national ACHD status for 19 CESEE countries from their ACHD representative based on an extensive survey for 2017 and/or 2018. Thirteen countries reported at least one tertiary ACHD centre with a median year of centre establishment in 2007 (interquartile range 2002–2013). ACHD centres reported a median of 2114 patients under active follow-up with an annual cardiac catheter and surgical intervention volume of 49 and 40, respectively. The majority (90%) of catheter or surgical interventions were funded by government reimbursement schemes. However, all 19 countries had financial caps on a hospital level, leading to patient waiting lists and restrictions in the number of procedures that can be performed. The median number of ACHD specialists per country was 3. The majority of centres (75%) did not have ACHD specialist nurses. The six countries with no dedicated ACHD centres had lower Gross Domestic Product per capita compared to the remainder (P = 0.005). Conclusion: The majority of countries in CESEE now have established ACHD services with adequate infrastructure and a patient workload comparable to the rest of Europe, but important gaps still exist. ACHD care is challenged or compromised by limited financial resources, insufficient staffing levels, and reimbursement caps on essential procedures compared to Western Europe. Active advocacy and increased resources are required to address the inequalities of care across the continent

Expression Quantitative Trait Loci Acting Across Multiple Tissues Are Enriched in Inherited Risk for Coronary Artery Disease.

-Despite recent discoveries of new genetic risk factors, the majority of risk for coronary artery disease (CAD) remains elusive. As the most proximal sensor of DNA variation, RNA abundance can help identify subpopulations of genetic variants active in and across tissues mediating CAD risk through gene expression