Congenital Heart Diseases: parental exposures and gene-environment interactions.

Congenital heart defects (CHDs) are the most prevalent of all birth defects, arising from the complex interplay of environmental exposures and genes. The molecular causes of most CHDs as well as the modifiable environmental risk factors, (especially for paternal exposure) remain largely unknown. Thus, there is an increasing interest in the study of gene-environment interaction in the pathogenesis of CHDs. The major aim of this project was to expand the knowledge of CHD etiology with specific attention at the identification of genetic and environmental risk factors. The effects of environmental factors might be modified by the genes responsible for the activation and detoxification of toxicant agents, contributing to an increased resistance (or sensitivity) to cardiac teratogenesis. Thus, the knowledge of genetic variants that can modify a person's risk of environmental exposure-induced disease may identify new potential therapeutic targets and appropriate preventive strategies. In the first part of the study, we analyzed the association between different parental environmental exposures and CHD risk. Moreover, it has been investigated if the presence of specific polymorphisms in genes involved in toxicant metabolism, glutathione-S transferase: GSTM1 and GSTT1, in the children might modulate the risk of CHD associated to toxicant exposure. In a case-control study , 360 parents of a child with CHD and 360 parents of a child without any congenital malformations, were compared in terms of lifestyle habits and toxicant exposures. The results showed that parental smoking (≥15 cigarettes/day) was significantly associated with CHD risk (OR 2.1, 95% CI 1.3-3.5, p=0.002). Moreover, both maternal (OR 2.6, 95% CI 1.6-4.2, p<0.0001) and paternal (OR 2.5, 95% CI 1.6-3.8, p<0.0001) occupational/environmental exposure to toxicants increased the risk of CHD. In addition, a significant additive risk (OR 4.5, 95% CI 2.5-8.3, p<0.0001) was found when both parents were exposed to toxicants. Regarding to genotype, GSTM1 and GSTT1 polymorphisms were investigated in 180 children with CHD. Both maternal (OR 3.6, 95% CI 1.1-11.2, p=0.03) and paternal (OR 3.3, 95% CI 1.0-10.8, p=0.03) exposure to toxicants increased the CHD risk in children who carried the combined null GST genotypes. The effect for the combined null genotypes was also stronger (OR 6.5, 95% CI 1.5-28.0, p=0.01) when both parents were exposed. In the second part of the project, we analyzed the joint effect of the glutathione-S transferase P1 (GSTP1) genetic polymorphism (Ile105Val) and maternal environmental exposure, on CHD risk. The GSTP1 gene is highly expressed early in fetal life and is the most abundant phase II xenobiotic metabolism enzyme in a human placenta. Fetal inherited GSTP1 Ile105Val polymorphism may modify the metabolism and excretion of xenobiotics from fetal tissue and increase the risk of CHD. In a case-control study, 190 children with CHD and 190 healthy children were genotyped for the GSTP1 Ile105Val polymorphism. All the mothers completed a structured questionnaire on the demographic as well as the preconceptional and lifestyle exposures. No significant differences in Ile105Val genotype frequencies were observed between CHD and healthy children (p=0.9) as well as no evidence of significant interaction between the maternal exposure and GSTP1 polymorphism was found. In the last part of the project, we investigated whether the ISL1 (rs1017) single-nucleotide polymorphism, in 3’-UTR region, conferred susceptibility to CHD. Indeed, the LIM homeodomain transcriptor factor ISL1 is a known marker for undifferentiated cardiac progenitor cells that give rise to both the right ventricle and the inflow and outflow tracts. To date, contradictory findings about the role of the ISL1 rs1017 single-nucleotide polymorphism on increased risk of CHD have been reported. In a case-control study, 309 patients with CHD and 500 healthy controls were genotyped for the ISL1 rs1017 polymorphism. No significant difference in the genotype and variant allele distribution was found between patients and controls. In addition, the ISL1 rs1017 polymorphism was not associated to the risk of CHD neither overall (p=0.7) nor stratifying the population by sex and CHD classification. All these findings suggest that common genetic variants, not necessarily disease-causing, may contribute to increase the risk of CHD, especially interacting with environmental factors. Further studies are required to better define the role of genetic factors and their potential interaction with environmental factors on the risk of CHD

Health Risk and Biological Effects of Cardiac Ionising Imaging: From Epidemiology to Genes

Cardiac diagnostic or therapeutic testing is an essential tool for diagnosis and treatment of cardiovascular disease, but it also involves considerable exposure to ionizing radiation. Every exposure produces a corresponding increase in cancer risk, and risks are highest for radiation exposure during infancy and adolescence. Recent studies on chromosomal biomarkers corroborate the current radioprotection assumption showing that even modest radiation load due to cardiac catheter-based fluoroscopic procedures can damage the DNA of the cell. In this article, we review the biological and clinical risks of cardiac imaging employing ionizing radiation. We also discuss the perspectives offered by the use of molecular biomarkers in order to better assess the long-term development of health effects

Le cardiopatie congenite: ruolo dei polimorfismi di GSTM1 e GSTT1 e di fattori ambientali nella loro insorgenza

Le cardiopatie congenite soni malformazioni del cuore o dei grandi vasi che colpiscono circa 8 bambini su 1000 nati vivi. Tra le varie cause una delle più frequenti è quella multifattoriale, cioè l' interazione tra fattori genetici predisponenti e fattori ambientali scatenanti. Per quanto riguarda i fattori ambientali sembrano essere coinvolte le esposizioni a fattori esterni dannosi di entrambi i genitori prima del concepimento. Per quanto concerne i fattori ambientali risultano essere coinvolti i polimorfismi dei geni di detossificazione GSTM1 e GSTT1

Solone: una banca dati delle norme per il patrimonio culturale. Roma e la Tarda Antichità

The Athenian statesman, lawmaker and poet Solon has given his name to a database related to the European legislation on art and cultural heritage. The database Solone, which is currently in progress and will be published on the Internet (http://solone.sns.it/), was designed and implemented by the LARTTE Laboratory (Interdisciplinary Centre for the Research, Planning, and Management of Cultural Heritage) of the Scuola Normale Superiore of Pisa. The database includes a selection of laws from the Roman period and Late Antiquity (from the 1st century B.C.E. to the 5th century C.E.), as well as from several countries that belong today to the European Community (Italy, France, United Kingdom, Spain, Greece), from the 19th century to 2006. In this database data on the individual norms and related institutions have been inserted. Bibliographic information was collected and the relationships between various laws, and the authorities and institutions that issued them have been considered. The database provides the full text of each law, often with one or more translations into Italian or English and a set of details regarding typologies, historical background, validity and jurisdiction, object, and sources. The database makes it possible to conduct research according to typologies, geographical areas or historical sections and institutions. In the present paper, Solone is presented from the perspective of one case study: the digital archive for the legislation on works of art, public and private buildings, roads and aqueducts enacted from the Roman Republic to the fourth Novel of Majorianus on public buildings issued in Ravenna in 459 C.E

MOONS: The New Multi-Object Spectrograph for the VLT

International audienceMOONS is the new Multi-Object Optical and Near-infrared Spectrograph currently under construction for the Very Large Telescope (VLT) at ESO. This remarkable instrument combines, for the first time, the collecting power of an 8-m telescope, 1000 fibres with individual robotic positioners, and both low- and high-resolution simultaneous spectral coverage across the 0.64–1.8 μm wavelength range. This facility will provide the astronomical community with a powerful, world-leading instrument able to serve a wide range of Galactic, extragalactic and cosmological studies. Construction is now proceeding full steam ahead and this overview article presents some of the science goals and the technical description of the MOONS instrument. More detailed information on the MOONS surveys is provided in the other dedicated articles in this Messenger issue