In silico analysis of TTR gene (coding and non-coding regions, and interactive network) and its implications in transthyretin-related amyloidosis.

Introduction: Transthyretin (TTR)-related amyloidosis is a life-threatening disease. Currently, several questions about the pathogenic mechanisms of TTR-related amyloidosis remain unanswered. Methods: We have investigated various TTR-related issues using different in silico approaches. Results: Using an amino acid similarity-based analysis, we have indicated the most relevant TTR secondary structures in determining mutation impact. Our amyloidogenic propensity analysis of TTR missense substitutions has highlighted a similar pattern for wild-type and mutated TTR amino b acid sequences. However, some mutations present differences with respect to the general distribution. We have identified non-coding variants in cis-regulatory elements of the TTR gene, and our analysis on V122I-related haplotypes has indicated differences in non-coding regulatory variants, suggesting differences among V122I carriers. The analysis of methylation status indicated CpG sites that may affect TTR expression. Finally, our interactive network analysis revealed functional partners of TTR that may play a modifier role in the pathogenesis of TTR-related amyloidosis. Discussion and conclusion: Our data provided new insights into the pathogenesis of TTR-related amyloidosis that, if they were to be confirmed through experimental investigations, could significantly improve our understanding of the disease

Human pharmacogenomic variation of antihypertensive drugs: from population genetics to personalized medicine.

AIM: To investigate the human pharmacogenetic variation related to antihypertensive drugs, providing a survey of functional interpopulation differences in hypertension pharmacogenes. MATERIALS & METHODS: The study was divided into two stages. In the first stage, we analyzed 1249 variants located in 57 hypertension pharmacogenes. This first-stage analysis confirmed that geographic origin strongly affects hypertension pharmacogenomic variation and that 31 pharmacogenes are geographically differentiated. In the second stage, we focused our attention on the ethnic-differentiated pharmacogenes, investigating 55,521 genetic variants. In silico analyses were performed to predict the effect of genetic variation. RESULTS: Our analyses indicated functional interpopulation differences, suggesting insight into the mechanisms of antihypertensive drug response. Moreover, our data suggested that rare variants mainly determine the functionality of genes related to antihypertensive drugs. CONCLUSION: Our study provided important knowledge about the genetics of the antihypertensive drug response, suggesting that next-generation sequencing technologies may develop reliable pharmacogenetic tests for antihypertensive drugs

Microparticles from dental calculus disclose paleoenvironmental and palaeoecological records

plants have always represented a key element in landscape delineation. Indeed, plant diversity, whose distribution is influenced by geographic/climatic variability, has affected both environmental and human ecology. the present contribution represents a multi-proxy study focused on the detection of starch, pollen and non-pollen palynomorphs in ancient dental calculus collected from pre-historical individuals buried at la sassa and pila archaeological sites (central Italy). the collected record suggested the potential use of plant taxa by the people living in central Italy during the copper-middle bronze age and expanded the body of evidence reported by previous palynological and palaeoecological studies. the application of a microscopic approach provided information about domesticated crops and/or gathered wild plants and inferred considerations on ancient environments, water sources, and past health and diseases. moreover, the research supplied data to define the natural resources (e.g., C4-plant intake) and the social use of the space during that period. another important aspect was the finding of plant clues referable to woody habitats, characterised by broad-leaved deciduous taxa and generally indicative of a warm-temperate climate and grassy vegetation. other unusual records (e.g., diatoms, brachysclereids) participated in defining the prehistoric ecological framework. thus, this work provides an overview on the potential of the human dental calculus analysis to delineate some features of the ancient plant ecology and biodiversity

Haplotype differences for copy number variants in the 22q11.23 region among human populations: a pigmentation-based model for selective pressure.

Two gene clusters are tightly linked in a narrow region of chromosome 22q11.23: the macrophage migration inhibitory factor (MIF) gene family and the glutathione S-transferase theta class. Within 120 kb in this region, two 30-kb deletions reach high frequencies in human populations. This gives rise to four haplotypic arrangements, which modulate the number of genes in both families. The variable patterns of linkage disequilibrium (LD) between these copy number variants (CNVs) in diverse human populations remain poorly understood. We analyzed 2469 individuals belonging to 27 human populations with different ethnic origins. Then we correlated the genetic variability of 22q11.23 CNVs with environmental variables. We confirmed an increasing strength of LD from Africa to Asia and to Europe. Further, we highlighted strongly significant correlations between the frequency of one of the haplotypes and pigmentation-related variables: skin color (R2=0.675, P<0.001), distance from the equator (R2=0.454, P<0.001), UVA radiation (R2=0.439, P<0.001), and UVB radiation (R2=0.313, P=0.002). The fact that all MIF-related genes are retained on this haplotype and the evidences gleaned from experimental systems seem to agree with the role of MIF-related genes in melanogenesis. As such, we propose a model that explains the geographic and ethnic distribution of 22q11.23 CNVs among human populations, assuming that MIF-related gene dosage could be associated with adaptation to low UV radiatio

Structures of (5′S)-8,5′-Cyclo-2′-deoxyguanosine Mismatched with dA or dT

pubs.acs.org/cr

The biological effects of diagnostic cardiac imaging on chronically exposed physicians: the importance of being non-ionizing

Ultrasounds and ionizing radiation are extensively used for diagnostic applications in the cardiology clinical practice. This paper reviewed the available information on occupational risk of the cardiologists who perform, every day, cardiac imaging procedures. At the moment, there are no consistent evidence that exposure to medical ultrasound is capable of inducing genetic effects, and representing a serious health hazard for clinical staff. In contrast, exposure to ionizing radiation may result in adverse health effect on clinical cardiologists. Although the current risk estimates are clouded by approximations and extrapolations, most data from cytogenetic studies have reported a detrimental effect on somatic DNA of professionally exposed personnel to chronic low doses of ionizing radiation. Since interventional cardiologists and electro-physiologists have the highest radiation exposure among health professionals, a major awareness is crucial for improving occupational protection. Furthermore, the use of a biological dosimeter could be a reliable tool for the risk quantification on an individual basis

Glutathione S-transferase gene polymorphisms and air pollution as interactive risk factors for asthma in a multicentre Italian field study: A preliminary study

Background: Asthma is one of the most common chronic diseases. Several studies have indicated that oxidative stress impairs pulmonary function. Glutathione S-transferases (GSTs) are believed to be critical in the protection of cells from reactive oxygen species. Aim: In this case-control study we analysed the possible association between polymorphism in several cytosolic GST genes, air pollution and asthma development. Methods: Genotyping of GSTM1 and GSTT1 genes was carried out by a multiplex PCR; GSTA1, GSTO1, GSTO2, GSTP1 polymorphisms were determined using the PCR-RFLP method. Data on atmospheric pollutants were collected by the regional air-quality monitoring network. Results: Among all the polymorphisms studied, the frequencies of GSTA1, GSTM1, GSTO2 and GSTT1 genotypes found in the group of asthmatic patients seem to differ from the frequencies of those found in the control group. Air pollutants were analysed and the air quality parameters considered proved to be significantly different, and therefore suitable for this study. Conclusion: The final result of this research should hopefully lead to a better understanding of gene– environment interactions, so allowing earlier prediction and diagnosis of asthma disease and providing an efficient means of prevention

Blood polymorphism frequencies in the T ofinu, the "Water Men" of Southern Benin

Informations on the genetic constitution (AcP, EsD, PGMl> AK, 6-PGD, Hb, Hp, Cp and Gc blood systems) of the Tofinu, a lacustrine population living in the pile-work of the Guinean coast (Southern Benin), are reported. The Tofinu gene fre¬quencies are much as would be expected from the geographical position of this country. The AcP, Hp and Hb fJ gene frequencies are compared with those of the other eth¬nic groups of Southern Benin as the Goun, Fon, Djedje, and Nago, using the contingen¬cy chi-square test of homogeneity. On the average, the five groups do not show any sig¬nificant differences. Thus it results that there seems to be a common genetic origin and that the cultural-linguistic differentiation followed the evolutive biological process for the populations of this country

The determination of the Cp and Hp polymorphisms

The phenotypes of the Cp and Hp serum polvmorphisms were de¬termined on a total of 22 Macaca fuscata fuscata. For the Cp types a single band was observed with a fast mobility in respect to the human Cp B band. Referring to the Hp system for some samples, in addition to the usual single band corresponding to the human Hp 1-1, one additional faint band which migrated in the approximate position of the slower¬moving human Hp 2-1 band was observed. Such a result is discussed