Presence Of Specific Genotypes Research Articles

Clinical and genetic features of arrhythmogenic cardiomyopathy: diagnosis, management and the heart failure perspective

BackgroundArrhythmogenic cardiomyopathy (ACM) is an emerging new concept of a life-threatening heart muscle disorder due not only to desmosome gene mutations but also to non-desmosome genes, such as filamin C, lamin A/C, phospholamban, transmembrane protein 43, titin, SCN5A, and RNA binding motif protein 20.Multi-modality imaging along with genetic testing are important tools for risk stratification to tailor treatment to a single patient. Cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE) is the gold standard for evaluating left and right ventricular structure and function, edema, and fibrosis. The identification of regional fibrosis with LGE has prognostic value.The management of ACM involves several aspects: treatment of arrhythmias and heart failure, risk stratification, implantable cardioverter-defibrillator (ICD) placement, exercise restrictions, and lifestyle changes. The decision for ICD placement in ACM patients is not well established and should be made weighing risks and benefits. However, the presence of specific genotypes can allow a precision medicine approach. In ACM patients with only mild left ventricular dysfunction but phospholamban, filamin C, or lamin A/C mutations, an ICD is now considered a reasonable approach. Aim of reviewWe sought to provide an overview of clinical and genetic features of arrhythmogenic cardiomyopathy providing epidemiology, imaging, diagnostic, and treatment information, using a systematic genetic approach. Key Scientific Concepts of ReviewACM is due not only to desmosome gene mutations but also to non-desmosome genes, such as filamin C, lamin A/C, phospholamban, transmembrane protein 43, titin, SCN5A, and RNA binding motif protein 20. The phenotypes of ACM spans from isolated right ventricular to biventricular or predominant left ventricular involvement. Due to heterogeneity, ACM remains an important diagnostic challenge requiring a multimodality imaging approach. -Genetic assessment may implement a precision medicine approach and should always be considered in the risk assessment and management.

Genotype-dependent associations between serotonin transporter gene (SLC6A4) DNA methylation and late-life depression

BackgroundDisrupted serotonergic signaling is often a feature of depression and the role of the serotonin transporter gene (SLC6A4), responsible for serotonin re-uptake, has received much attention in this regard. Most studies have focused on the polymorphic 5-HTTLPR upstream repeat, or DNA methylation at the promoter CpG island. Few studies have explored the influence of genetic variation across the gene on DNA methylation, and their combined association with depression risk. The aim of this study was to determine whether genetic variation in the SLC6A4 gene influences promoter DNA methylation, and whether these are associated with depression status.MethodThe ESPRIT study involves a community-based population of older individuals (> 65 years of age). Major depressive disorder (MDD) was diagnosed according to DSM-IV (American Psychiatric Association, 1994) criteria, and severe depressive symptoms assessed by the Centre for Epidemiological Studies Depression (CES-D) Scale. Sequenom MassARRAY was used to measure SLC6A4 methylation status (n = 302).ResultsNominally significant associations were observed between SLC6A4 genetic variants (5-HTTLPR, rs140700, rs4251417, rs6354, rs25528, rs25531) and DNA methylation at several CpG sites. In multivariate regression, DNA methylation was associated with depression status, but only in the presence of specific genotypes. In individuals homozygous for the short 5-HTTLPR and 5-HTTLPR/r25531 alleles, lower methylation at two CpGs was associated with depression (β = − 0.44 to β = − 0.31; p = 0.001 to p = 0.038).ConclusionWe present evidence for genotype-dependent associations between SLC6A4 methylation and depression. Genetic variants may also play a role in influencing promoter methylation levels and its association with depression.

Genetically determined enlargement of carotid body evaluated using computed angiotomography

It has recently been established that carotid bodies play a significant role in the regulation of activities of the cardiovascular system as well as in the pathogenesis of arterial hypertension, heart failure and diabetes. Aim of study was to determinate the influence of polymorphisms within genes of the renin-angiotensin-aldosterone system (RAAS) on the volume of the carotid bodies (CB) in patients with hypertension (HTA).The study group consisted of 77 patients with HTA. All patients were genotyped for single-nucleotide polymorphisms of genes coding for: angiotensinogen: rs4762, rs5049, rs5051 and rs699; angiotensin-converting enzyme: rs4343; angiotensin receptor type 1 gene (AGTR1): rs5182 and rs5186; and the aldosterone synthase: rs1799998. The estimation of volumes of CB (VrCB+lCB) was based on computed tomography angiography.Among individuals with essential hypertension certain relationships were documented between rs5182 and rs5186 polymorphisms of AGTR1 gene and rs1799998 polymorphism of CYP11B2 gene on one hand and the volume of carotid bodies on one other. Patients carrying the C alleles within the rs5182 and rs5186 of AGTR1 gene was associated with higher values of VrCB+lCB. The carriage of the T allele in the rs5182 locus of the AGTR1 gene determine lower values of VrCB+lCB.In summary, in patients with HTA a higher volume of CB may be resulted from the presence of specific genotypes in RAAS.

Spatial distribution of Legionella pneumophila MLVA-genotypes in a drinking water system

Bacteria of the genus Legionella cause water-based infections, resulting in severe pneumonia. To improve our knowledge about Legionella spp. ecology, its prevalence and its relationships with environmental factors were studied. Seasonal samples were taken from both water and biofilm at seven sampling points of a small drinking water distribution system in Israel. Representative isolates were obtained from each sample and identified to the species level. Legionella pneumophila was further determined to the serotype and genotype level. High resolution genotyping of L. pneumophila isolates was achieved by Multiple-Locus Variable number of tandem repeat Analysis (MLVA). Within the studied water system, Legionella plate counts were higher in summer and highly variable even between adjacent sampling points. Legionella was present in six out of the seven selected sampling points, with counts ranging from 1.0 × 101 to 5.8 × 103 cfu/l. Water counts were significantly higher in points where Legionella was present in biofilms. The main fraction of the isolated Legionella was L. pneumophila serogroup 1. Serogroup 3 and Legionella sainthelensis were also isolated. Legionella counts were positively correlated with heterotrophic plate counts at 37 °C and negatively correlated with chlorine. Five MLVA-genotypes of L. pneumophila were identified at different buildings of the sampled area. The presence of a specific genotype, “MLVA-genotype 4”, consistently co-occurred with high Legionella counts and seemed to “trigger” high Legionella counts in cold water. Our hypothesis is that both the presence of L. pneumophila in biofilm and the presence of specific genotypes, may indicate and/or even lead to high Legionella concentration in water. This observation deserves further studies in a broad range of drinking water systems to assess its potential for general use in drinking water monitoring and management.

Prognostic factors for the late onset Pompe disease with enzyme replacement therapy: From our experience of 4 cases including an autopsy case

We report 4 cases of late onset glycogen storage disease type II (GSD II) or Pompe disease (OMIM #232300), under enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rh-GAA, OMIM ∗606800). In these 4 cases, we focused on the case of a 28-years-old man, whose condition at the ERT starting was the worst and resulted in poor prognosis. The autopsy was done under his family’s permission, and revealed severe accumulation of glycogen in his muscle, especially diaphragm or iliopsoas, and pulmonary veno-occlusive disease (PVOD) which resulted in severe pulmonary hypertension (PH). This is the first report of PVOD as the cause of PH in Pompe disease. We studied this case comparing to another 3 cases of late onset Pompe disease under the same course of ERT in our hospital, and the average data of the group of late onset Pompe disease with severe pulmonary insufficiency receiving ERT, supposed that low score of the body mass index (BMI) on the baseline, the presence of specific genotype (p.R600C), and signs of pulmonary dysfunction suggesting PH (tachypnea, ultrasound cardiography data) were factors that influenced the prognosis. For a better prognosis in the late onset Pompe disease, an early diagnosis for the early start of ERT before the onset of respiratory failure should be important, and the deliberate management and care should be needed even after the ERT start, especially for severe cases including pulmonary dysfunction.

Abacavir: it’s use and hypersensitivity

Abacavir, a nucleoside reverse transcriptase inhibitor, is useful in first and second line therapy as well as a substitute for Stavudine and Zidovudine for toxicity. Although safe and well tolerated, a life threatening hypersensitivity reaction can occur. The risk for developing this reaction relates to the presence of specific genotypes especially HLA-B*5701.