Emanuela Medda

Endometriosis and Organochlorinated Environmental Pollutants: A Case–Control Study on Italian Women of Reproductive Age

Background Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting. Objective We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis. Methods We conducted a case–control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p′-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. Results We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs. Conclusions The results of this study show that an association exists between increased PCB and p,p′-DDE serum concentrations and the risk of endometriosis.

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

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.

Family planning KAP survey in Gaza.

This study explores the reproductive attitudes, contraceptive use, demand for family planning and related topics of a representative sample of the female population of reproductive age resident in a Refugee Camp in the Gaza Strip. A cluster sample of 841 resident women of reproductive age (15-49 years) was interviewed in their homes. Univariate and multivariate statistical analyses were performed using BMDP software. 98% of the interviewees favour family planning and 88% plan to use a contraceptive in the future. However, 52% of the women at risk do not use any contraception because of their husbands opposition, fear of side effects or lack of knowledge. The risk of having seven or more children is positively associated with a womans low educational level and husbands desire for more than seven children. Despite favourable attitudes regarding family planning, there is ignorance and the prevalence of contraception use is low. There is a gap between fertility preference and achievement.

Congenital Hypothyroidism due to Defects of Thyroid Development and Mild Increase of TSH at Screening: Data From the Italian National Registry of Infants With Congenital Hypothyroidism

CONTEXT Over the years lower TSH cutoffs have been adopted in some screening programs for congenital hypothyroidism (CH) worldwide. This has resulted in a progressive increase in detecting additional mild forms of the disease, essentially with normally located and shaped thyroid. However, the question of whether such additional mild CH cases can benefit from detection by newborn screening and early thyroid hormone treatment is still open. OBJECTIVE The aim of this study was to estimate the frequency of cases with mild increase of TSH at screening in the Italian population of babies with permanent CH and to characterize these babies in terms of diagnosis classification and neonatal features. METHODS Data recorded in the Italian National Registry of infants with CH were analyzed. RESULTS Between 2000 and 2006, 17 of the 25 Italian screening centers adopted a TSH cutoff at screening of <15.0 μU/mL. It was found that 21.6% of babies with permanent CH had TSH at screening of 15.0 μU/mL or less, whereas this percentage was 54% in infants with transient hypothyroidism. Among the babies with permanent CH and mild increase of TSH at screening (≤15 μU/mL), 19.6% had thyroid dysgenesis with serum TSH levels at confirmation of the diagnosis ranging from 9.9 to 708 μU/mL. These babies would have been missed at screening if the cutoff had been higher. CONCLUSIONS Lowering TSH cutoff in our country has enabled us to detect additional cases of permanent CH, a number of which had defects of thyroid development and severe hypothyroidism at confirmation of the diagnosis.

Heritability and shared genetic effects of asthma and hay fever: an Italian study of young twins.

A 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.

An association analysis of microsatellite markers across the Prader-Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum disorder

Autism (OMIM 209850) is a neurodevelopmental disorder with a significant genetic component of a complex nature. Cytogenetic abnormalities in the Prader–Willi/Angelman syndrome critical region (PWACR) on chromosome 15 (q11‐13) have been described in several individuals with autism. We have examined five microsatellite markers spread across the 4 Mb PWACR for linkage disequilibrium (LD) in 148 families with autism spectrum disorder (ASD) and a subset of 82 families with autism using the extended transmission disequilibrium test (ETDT). The markers examined were D15S11, D15S128, D15S1506, GABRB3, and D15S1002. In addition we have examined the microsatellite D15S822 for hemizygous deletion status in our sample as it had been previously reported to be increased in autism. We found no significant LD with any of the markers tested either in the ASD or autism families when looking at paternal and maternal meioses combined. However, as there are known imprinted genes in the region, including possibly GABRB3, we also examined for LD in paternal and maternal meioses separately. Examining paternal transmissions only, we found marginal evidence for LD with a protective allele at marker D15S11 in the ASD families (Chi‐sq 7 df, P = 0.05) and marginal evidence for risk alleles at markers D15S1506 (Chi‐sq 13.7, 6 df, P = 0.06), GABRB3 (Chi‐sq 15.9, 8 df, P = 0.11) and D15S1002 (Chi‐sq 17.7, 9 df, P = 0.08) in the autism only families. The allele responsible for the association with GABRB3 is the 191 allele which was previously reported to be overtransmitted. Hemizygous deletion of the microsatellite D15S822 was found in 3 out of 340 independent chromosomes in our sample; a rate of 0.8%. This is not significantly different to the frequency in the general population. In conclusion, our results did not rule out the involvement of this chromosomal region, but provided further evidence, albeit very limited, to implicate GABRB3. Further more systematic work in larger samples is required and confirmation that GABRB3 is imprinted is desirable.

An update on the Italian Twin Register: advances in cohort recruitment, project building and network development.

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 enrollment 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.

Heritability of central blood pressure and arterial stiffness: a twin study.

Objective: Central blood pressure and aortic stiffness have been consistently reported as strong cardiovascular risk factors. Twin studies by comparing identical with nonidentical twins produce information on the relative contribution of genes and environment. Methods: One hundred and fifty-four monozygotic (MZ) and 42 dizygotic (DZ) twin pairs (age 43 ± 17 years) from Hungary and the United States underwent brachial and central augmentation index (AIx), brachial and central pressure, and aortic pulse wave velocity (PWV) measurements with the invasively validated Arteriograph device. Bivariate Cholesky decomposition models were applied. Results: Age-adjusted, sex-adjusted and country-adjusted heritability was 60.0% for central SBP [95% confidence interval (CI), 44.8–69.6%], 50.1% for aortic PWV (95%CI, 26.0–66.8%), 48.7% for aortic AIx (95%CI, 1.7–74.0%), 46.8% for brachial AIx (95%CI, 1.1–73.8%), 46.7% for central pulse pressure (PP) (95%CI, 12.4–61.4%), and 30.0% for brachial PP (95%CI, 0.0–53.4%). Central SBP and PP had strong bivariate correlations with brachial (r = 0.461 and 0.425) and central AIx (r = 0.457 and 0.419), as well as with aortic PWV (r = 0.341 and 0.292, all P < 0.001). Brachial PP had a weak correlation with brachial AIx (r = −0.118, P < 0.05), central AIx (r = −0.122, P < 0.05), and none with aortic PWV (r = 0.08, P = n.s.). Genetic factors explained a moderate phenotypic correlation between central PP, SBP, brachial SBP and aortic PWV. Conclusions: Central systolic and PPs, brachial PP, AIx, aortic PWV are moderately heritable. A moderate genetic covariance among aortic PWV and central PP, central SBP and brachial SBP was found.

Multiple factors influencing the incidence of congenital hypothyroidism detected by neonatal screening.

Background/Aims: Over the years a rise in the incidence of congenital hypothyroidism (CH) has been described worldwide. The aim of our study was to investigate trends in the incidence of CH in Italy over the period 1987-2008, and to investigate which factors may have influenced the CH incidence in our country. Methods: Data were derived from the Italian National Registry of Infants with Congenital Hypothyroidism. Since 1998 the laboratory procedures related to neonatal screening for CH have changed drastically. Accordingly, we estimated the CH incidence during the period 1987-1998 (period 1) and the period 1999-2008 (period 2). Results: The incidence of CH confirmed at birth (including transient hypothyroidism) has increased from 1:3,000 liveborn infants in period 1 to 1:1,940 in period 2 (+54%), whereas the incidence of purely permanent CH increased from 1:3,200 to 1:2,320 (+38%). Lowering of the TSH cutoff was the most important factor contributing to the increase of CH incidence in Italy. Moreover, an increment of 58% of preterm babies with permanent CH was found in period 2 compared with period 1. Conclusion: Our results suggest that more than one cause is responsible for the rise in the increasing CH incidence, with lowering of the screening TSH cutoff and an increased survival rate of a growing number of preterm babies both playing an important role.

Much More than Model Fitting? Evidence for the Heritability of Method Effect Associated with Positively Worded Items of the Life Orientation Test Revised.

When a self-report instrument includes a balanced number of positively and negatively worded items, factor analysts often use method effect factors to aid model fitting. One of the most widely investigated sources of method effects stems from the respondent tendencies to agree with an item regardless of its content. The nature of these effects, often referred to as acquiescence, is still debated. This study provides a unique contribution to the understanding of the substantive nature of these factors. The revised Life Orientation Test was administered to 653 twins (40% males) to unravel the genetic and the environmental components of method effect associated with positively worded items. Biometric modeling revealed significant heritability for the method effect factor along with strong unique environmental influences. This provides a substantive interpretation of method effects as a stable individual tendency. Theoretical and practical implications of the findings are discussed.