TNFRSF1B +676 T>G polymorphism predicts survival of non-Small cell lung cancer patients treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>The dysregulation of gene expression in the TNF-TNFR superfamily has been involved in various human cancers including non-small cell lung cancer (NSCLC). Furthermore, functional polymorphisms in <it>TNF-α </it>and <it>TNFRSF1B </it>genes that alter gene expression are likely to be associated with risk and clinical outcomes of cancers. However, few reported studies have investigated the association between potentially functional SNPs in both <it>TNF-α </it>and <it>TNFRSF1B </it>and prognosis of NSCLC patients treated with chemoradiotherapy.</p> <p>Methods</p> <p>We genotyped five potentially functional polymorphisms of <it>TNF-α </it>and <it>TNFRSF1B </it>genes [<it>TNF-α </it>-308 G>A (rs1800629) and -1031 T>C (rs1799964); <it>TNFRSF1B </it>+676 T>G (rs1061622), -1709A>T(rs652625) and +1663A>G (rs1061624)] in 225 NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard models were used to evaluate associations between these variants and NSCLC overall survival (OS).</p> <p>Results</p> <p>We found that the <it>TNFRSF1B </it>+676 GG genotype was associated with a significantly better OS of NSCLC (GG <it>vs. </it>TT: adjusted HR = 0.38, 95% CI = 0.15-0.94; GG <it>vs. </it>GT/TT: adjusted HR = 0.35, 95% CI = 0.14-0.88). Further stepwise multivariate Cox regression analysis showed that the <it>TNFRSF1B </it>+676 GG was an independent prognosis predictor in this NSCLC cohort (GG <it>vs. </it>GT/TT: HR = 0.35, 95% CI = 0.14-0.85), in the presence of node status (N_2-3<it>vs. </it>N_0-1: HR = 1.60, 95% CI = 1.09-2.35) and tumor stage (T_3-4<it>vs. </it>T_0-2: HR = 1.48, 95% CI = 1.08-2.03).</p> <p>Conclusions</p> <p>Although the exact biological function for this SNP remains to be explored, our findings suggest a possible role of <it>TNFRSF1B </it>+676 T>G (rs1061622) in the prognosis of NSCLC. Further large and functional studies are needed to confirm our findings.</p

Huntington disease: Genetics, prevention, and therapy approaches

Huntington’s chorea or Huntington disease (HD) is a late-onset autosomal dominant neurodegenerative disorder caused by a trinucleotide repeat expansion. The multidisciplinary study of HD has been the focus of an international collaborating effort of basic and applied research for several decades. HD was the first human genetic disease mapped using linkage analysis of DNA polymorphisms and became a paradigm for scores of genes mapped in the same manner. Presymptomatic and prenatal testing have been available for HD families in the last 30 years, following genetic counseling and careful bioethical guidelines. Nevertheless, with the cure for the disease still elusive the uptake of predictive testing by at risk individuals is low. Current treatment of HD is mostly symptomatic, but ongoing observational studies, clinical trials and development of new gene silencing technologies have provided hopeful results. © Springer International Publishing AG 2017

Cerebral thrombosis: A neurogenetic approach

Cerebral venous thrombosis (CVT) is a severe multifactorial condition with various clinical manifestations that may include headache, papilledema, seizures, focal deficits, coma and death. The mortality rate of untreated CVT is up to 50%, but it drops to 10% when CVT is properly treated. Prevention of CVT is feasible through healthy lifestyle, genetic counseling, molecular genetic analysis for common thrombophilia-related mutations, and prophylactic anticoagulative medication. © Springer International Publishing AG 2017

The Role of MicroRNAs in Thrombosis

MicroRNAs (miRNAs) are small noncoding regulatory RNA molecules that play a significant role in targeted downregulation of gene expression by RNA silencing and posttranscriptional regulation. Mounting evidence of recent studies indicates that there is dysregulation of expression level of a wide range of miRNAs in a variety of cardiovascular diseases related to thrombosis including venous thromboembolism, coronary artery disease, stroke, and myocardial infarction. In this review, the current knowledge on the role of miRNAs in thrombosis is discussed. Future research may further unravel the involvement of miRNAs in the pathogenesis of thrombosis as well as possibly clarify the clinical usefulness of miRNAs as biomarkers and potential therapeutic targets. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG

Use of truncated pyramid representation methodology in three-dimensional reconstruction: an example

This paper describes a new methodology for three-dimensional (3D) representation of biological structures contained in a series of sections, using an illustrative example. Spatial reconstruction of a specific area of an astrocytoma biopsy was carried out with alignment of the serial sections at an accuracy of 0.01% (or 1 mum cm(-1)), using the truncated pyramid representation (TPR) methodology. TPR includes: (a) serial tissue sectioning in a ribbon form; (b) alignment of the serial sections based on the properties of a ‘truncated pyramid’; (c) identification and localization of structures in every section using a field frame, and representation of the contours of the structures in every section as topographic contours (charting); (d) artificial reconstruction of the missing space between serial sections, by drawing intermediate contours based on the prototype contours of successive sections in order to provide smoother and more elegant representation of the volumes (complementation); and (e) 3D reconstruction. Application of TPR in a selected area of the astrocytoma enabled us to observe the morphology and spatial distribution of neoplastic astrocytic nuclei, which encircled an adjacent blood vessel

Neurofibromatosis-noonan syndrome: A possible paradigm of the combination of genetic and epigenetic factors

Neurofibromatosis-Noonan syndrome (NFNS) is a clinical entity possessing traits of autosomal dominant disorders neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). Germline mutations that disrupt the RAS/MAPK pathway are involved in the pathogenesis of both NS and NF1. In light of a studied Greek family, a new theory for etiological pathogenesis of NFNS is suggested. The NFNS phenotype may be the final result of a combination of a genetic factor (a mutation in the NF1 gene) and an environmental factor with the epigenetic effects of muscle hypotonia (such as hydantoin in the reported Greek family), causing hypoplasia of the face and micrognathia. © Springer International Publishing AG 2017

The Impact of ACE and ACE2 Gene Polymorphisms in Pulmonary Diseases including COVID-19

Chronic and acute respiratory diseases pose a major problem for public health worldwide due to the high morbidity and mortality rates, while treatment options remain mostly symptomatic. The renin-angiotensin system (RAS) plays an important role in lung tissue, regulating pulmonary circulation and blood pressure, but also contributing to normal pulmonary function and development. Angiotensin-converting enzyme (ACE) and its homologous angiotensin-converting enzyme 2 (ACE2) are considered to be amongst the main RAS regulators and are highly expressed in the pulmonary vascular endothelium. This review discusses the impact of ACE and ACE2 functional gene polymorphisms on seven major pulmonary diseases, in terms of predisposition, course, and outcome, revealing their potential utility as both genetic markers and biomarkers. The discussed conditions include chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), asthma, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), lung cancer and pulmonary sarcoidosis (PS), as well as SARS-CoV-2 viral infection and COVID-19 disease. © 2022 International Institute of Anticancer Research. All rights reserved

Prenatal Genetic Testing for X-Linked Hypohidrotic Ectodermal Dysplasia

Introduction: Hypohidrotic ectodermal dysplasia (HED) is an X-linked recessive disorder, characterised by abnormally developed ectodermal tissues (sweat glands, enamel, hair, nails). HED is caused by mutations of the EDA1 gene (Xq13.1) which codes for ectodysplasin A, a transmembrane signalling protein, which plays a significant role in ectodermal differentiation. Here we present a case of prenatal testing for HED. Methods: An 11-month-old boy with no family history was clinically diagnosed with HED. Genomic DNA was isolated from the patient’s white blood cells, and the possible existence of mutations suspected for HED development was investigated by an NGS gene panel. Total DNA was also isolated from blood samples of his parents. After mutation detection and genetic counselling, a prenatal HED test was performed during the 12th week of the mother’s next pregnancy. Embryonic DNA was isolated from a sample of chorionic villi. Parts of the EDA1, AMELX (X chromosome), and SRY (Y chromosome) genes were amplified by PCR, using the corresponding primers. Results: The boy with HED was found to be a hemizygote for the c.595_613del (p. Pro199PhefsTer75) deletion in the EDA1 gene. The fetus was male (XY) that did not carry the pathological mutation. Conclusion: The initial diagnosis of a family member with HED in a case with no family history poses the question whether this type of ectodermal dysplasia is autosomal dominant (and the case is due to a de novo mutation), autosomal recessive, or X-linked recessive. Molecular detection of the responsible mutation allows proper genetic counselling, carrier testing, and prevention by prenatal testing. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG

The angiotensin-converting enzyme insertion/ deletion polymorphism as a common risk factor for major pregnancy complications

Idiopathic pregnancy complications pose a major threat to both maternal and fetal health worldwide. Numerous studies have implicated the role of the renin-angiotensin system (RAS) in the development of obstetric syndromes, since it is crucial for the uteroplacental function. A major RAS component is the angiotensin-converting enzyme (ACE), which hydrolyses angiotensin I to angiotensin II, and not only regulates arterial pressure, but also fibrinolytic activity, indirectly, through the expression of plasminogen activator inhibitor-1. A key functional polymorphism of the ACE gene is the insertion/deletion (I/D) polymorphism, which affects gene expression and product levels, and can therefore lead to high blood pressure and/or reduced fibrinolytic activity. These can cause major pregnancy complications, such as preeclampsia, recurrent pregnancy loss and preterm birth. This review discusses how the ACE I/D is associated with susceptibility towards pregnancy complications, on its own or in combination with other functional gene polymorphisms such, as the angiotensin II receptor type 1 (AT1R) A1166CC, angiotensin II receptor type 2 (AT2R) G1332A, plasminogen activator inhibitor-1 (PAI-1) 4G/5G, matrix metallopeptidase- 9 (MMP-9) C1562T, angiotensinogen (AGT) M235T, renin (REN) 83A/G, factor XIII (F13) Val34Leu and endothelial nitric oxide synthase (eNOS) 4a/b. © 2021 International Institute of Anticancer Research. All rights reserved