Suchergebnisse

Carotid atherosclerosis (CAS) is associated with increased cardiovascular risk, and therefore, assessing the genetic versus environmental background of CAS traits is of key importance. Carotid intima-media-thickness and plaque characteristics seem to be moderately heritable, with remarkable differences in both heritability and presence or severity of these traits among ethnicities. Although the considerable role of additive genetic effects is obvious, based on the results so far, there is an important emphasis on non-shared environmental factors as well. We aimed to collect and summarize the papers that investigate twin and family studies assessing the phenotypic variance attributable to genetic associations with CAS. Genes in relation to CAS markers were overviewed with a focus on genetic association studies and genome-wide association studies. Although the role of certain genes is confirmed by studies conducted on large populations and meta-analyses, many of them show conflicting results. A great focus should be on future studies elucidating the exact pathomechanism of these genes in CAS in order to imply them as novel therapeutic targets.

AbstractA number of studies have provided evidence of a significant familial aggregation for both asthma and hay fever, and have reported a substantial comorbidity between the two conditions. However, far fewer, especially in Italy, have aimed at clarifying the origins of such comorbidity. The main aims of the present study were (a) to estimate heritability of asthma and hay fever, (b) to measure the association between asthma and hay fever at the individual level, and (c) to assess the extent to which genetic and environmental factors, shared by the two conditions, mediate this association. The twin method was used. The study sample was derived from the Italian Twin Registry, and included 392 twin pairs aged 8 to 17 years. Data collection was performed through parent self-administered questionnaire. Bivariate structural equation twin modeling was applied to asthma and hay fever. Genetic factors accounted for 92% and 78% of the variance in liability to asthma and hay fever, respectively, with the remaining contributions due to unique environmental influences. The within-individual association between asthma and hay fever was substantial. The genetic correlation between the two conditions was .58, whereas no evidence of overlapping unique environmental effects was found. In conclusion, this study showed a high heritability of asthma and hay fever in the Italian child and adolescent population. It also indicated that asthma and hay fever share, to a large extent, a common genetic background, and environmental factors are not relevant to explain the comorbidity.

AbstractThe Italian Twin Registry (ITR), established in 2001, is a population-based registry of voluntary twins. To date, it consists of approximately 29,000 twins who gave their consent to participate in the studies proposed by the ITR research group. The database comprises 11,500 monozygotic and 16,700 dizygotic twins resident throughout the country and belonging to a wide age range (from 0 to 95 years, mean 36.8 years). This article provides an overview of the recruitment strategies along with the major phenotypes investigated during an 18 years' research period. Over the years, several self-reported questionnaire data were collected, together with saliva/blood samples and measurements taken during in-person interviews or outpatient clinical examinations. Mental and behavioral phenotypes as well as atherosclerotic traits were studied in depth across different age groups. A birth cohort of twins was established and followed up. Novel research hypotheses are also being tested in ongoing projects. The ITR is involved in international studies in collaboration with other twin registries and represents a valuable resource for national and international research initiatives regarding a broad spectrum of health-related characteristics.

The Italian Twin Register has been in place for more than 10 years. Since its establishment, it has been focusing, on the one hand, on a continuous update of the existing information, and on the other hand, on new phenotypes and sample collection. Demographic data on about 140,000 twins have been updated using the municipality registries. The Italian Twin Register has been carrying out several new studies during the last few years. A birth cohort of twins, Multiple Births Cohort Study, has been started and the enrolment is ongoing. For this cohort, data on pregnancy and birth are collected, and periodical follow-ups are made. DNA is being collected for the twins and their parents. In the area of behavioral genetics, most efforts have been directed to psychological well being assessed with self-reported tools. Research on age-related traits continues with studies on arteriosclerosis development, early biomarkers in mild cognitive impairment, and the relation between lifestyle habits and mutagen sensitivity. The Italian Twin Register biobanking has grown in its size and in its know-how in terms of both technical issues and ethical procedures implementation. Furthermore, attitudes toward biobank-based research, together with willingness and motivation for donation, are being investigated. A valuable key resource for the Italian Twin Register is the possibility of linking twin data with disease registries. This approach has been yielding several important results, such as the recent study on the heritability of type 1 diabetes.

Background: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes. Methods: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow. Results: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants. Conclusion: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants.

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors. ; We thank Ronnie Lendrum for manuscript preparation and Tim Triche Jr. for his invaluable advice. This work has been financially supported by the Plan Nacional de I+D+I 2008-2011/2013-2016/FEDER (PI11/01728 to A.F.F., PI 12/0615 to J.A.R., PI10/0449 to P.M., and PI11/0119 to C.B.); the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (Miguel Servet contracts CP11/00131 to A.F.F. and CP07/0059 to C.B.); the Spanish Ministry of Health (PS09/02454 and PI12/01080 to M.F.F.); the Spanish National Research Council (CSIC; 200820I172 to M.F.F.); IUOPA (to C.F. and G.F.B.); Fundacion Cientifica de la AECC (to R.G.U. and P.M.); Fundación Ramón Areces (to M.F.F.); and FICYT (to E.G.T.). J.G.-C. receives funding from the Fondo de Investigaciones Sanitarias (FIS; PI05/2217 and PI08/0029) and the Madrid Regional Government (S-BIO-0204-2006 and S2010/BMD-2420). J.A.R. receives funding from the Fondo de Investigaciones Sanitarias (ISCIII-FIS PI 12/0615). P.M. is also supported by MINECO (SAF2013/43065), ERANET E-Rare (PI112/03112), and Fundación Sandra Ibarra. P.M. also acknowledges support from Obra Social "La Caixa/Fundacio Josep Carreras." The IUOPA is supported by the Obra Social Cajastur, Spain. ; Sí

Il programma di iodoprofilassi è stato introdotto in Italia a seguito dell'approvazione della Legge 55/2005 "Disposizioni finalizzate alla prevenzione del gozzo endemico e di altre patologie da carenza iodica", con la quale si definiscono le modalità di utilizzo e di vendita del sale iodato. A supporto dello strumento legislativo, nel 2009 è stato istituito, presso l'Istituto Superiore di Sanità, l'Osservatorio Nazionale per il Monitoraggio della Iodoprofilassi in Italia (OSNAMI). L'OSNAMI, in collaborazione con gli Osservatori Regionali per la Prevenzione del Gozzo, ha il compito di verificare l'efficienza e l'efficacia del programma nazionale di iodoprofilassi e di fornire informazioni utili per eventuali azioni correttive. A tale scopo, tra il 2007 e il 2012 l'OSNAMI ha effettuato un primo monitoraggio condotto su 7455 bambini in età scolare. In quegli anni la vendita di sale iodato in Itali era inferiore al 50% di tutto il sale venduto e l'analisi degli indicatori specifici (ioduria, frequenza di gozzo in età scolare e TSH neonatale) aveva dimostrato il persistere di una lieve carenza nutrizionale di iodio nel nostro Paese. Infatti la concentrazione mediana di iodio urinario (Urinary Iodine Concentration, UIC) era risultata indicativa di iodo-sufficienza solo in tre (Liguria, Toscana, Sicilia) delle nove regioni esaminate (Piemonte, Lombardia, Veneto, Molise, Puglia, Calabria), mentre la prevalenza del gozzo era superiore al valore soglia del 5% in tutte le 6 regioni che avevano fornito i dati (Liguria, Emilia-Romagna, Marche, Toscana, Calabria, Sicilia). In accordo con gli altri indicatori, anche la frequenza di valori elevati di TSH neonatale (5.9% nel 2015) aveva confermato una lieve carenza nutrizionale di iodio nella popolazione neonatale. Infine, l'analisi delle prescrizioni di farmaci anti-tiroidei (metimazolo), quale misura indiretta dei nuovi casi di iperttiroidismo nella popolazione, di fatto non aveva mostrato variazioni significative nel numero di prescrizioni nel periodo 2006-2012 rispetto al passato, anche se Bolzano, dove la iodoprofilassi è attiva da circa 40 anni, risultava ancora la provincia con il più basso numero di prescrizioni per abitante. Sulla base di questi risultati, la Direzione Generale per l'Igiene e la Sicurezza degli Alimenti e la Nutrizione (DGISAN) del Ministero della Salute insieme al panel di esperti dell'OSNAMI hanno deciso di intensificare le campagne informative per la promozione del programma di iodoprofilassi attraverso la diffusione dello slogan poco sale ma iodato, in accordo con la strategia di riduzione del consumo di sale, già attuata a livello nazionale dal Ministero della Salute. Tali sforzi, supportati anche dal continuo impegno nel promuovere il programma di iodoprofilassi da parte di Associazioni dei Pazienti, Società Scientifiche, medici dei Servizi per l'Igiene degli Alimenti e la Nutrizione (SIAN), hanno portato al raggiungimento della iodosufficienza, così come dimostrato dai risultati della seconda sorveglianza OSNAMI riportati qui di seguito come dati nazionali e nell'intero volume con dettaglio regionale.