Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for "inflamm-aging".

Mitochondrial components, including mitochondrial DNA (mtDNA), when released extracellularly, can act as "damage-associated molecular pattern" (DAMP) agents and cause inflammation. As many elderly people are characterized by a low-grade, chronic inflammatory status defined "inflamm-aging," we evaluated if circulating mtDNA can contribute to this phenomenon. Eight hundred and thirty-one Caucasian subjects were enrolled in the study, including 429 siblings aged 90-104 (90+ siblings). mtDNA plasma levels increased gradually after the fifth decade of life. In 90+ subjects, mtDNA values of two members of the same sibling relationship were directly correlated, suggesting a role for familiar/genetic background in controlling the levels of circulating mtDNA. The subjects with the highest mtDNA plasma levels had the highest amounts of TNF-α, IL-6, RANTES, and IL-1ra; the subjects with the lowest mtDNA levels had the lowest levels of the same cytokines. In vitro stimulation of monocytes with mtDNA concentrations similar to the highest levels observed in vivo resulted in an increased production of TNF-α, suggesting that mtDNA can modulate the production of proinflammatory cytokines. Our findings therefore show that circulating mtDNA increases with age, and can significantly contribute to the maintenance of the low-grade, chronic inflammation observed in elderly people.

Piccolipiù, a multicenter birth cohort in Italy: protocol of the study.

BACKGROUND: The fetal and infant life are periods of rapid development, characterized by high susceptibility to exposures. Birth cohorts provide unique opportunities to study early-life exposures in association with child development and health, as well as, with longer follow-up, the early life origin of adult diseases. Piccolipiù is an Italian birth cohort recently set up to investigate the effects of environmental exposures, parental conditions and social factors acting during pre-natal and early post-natal life on infant and child health and development. We describe here its main characteristics. METHODS/DESIGN: Piccolipiù is a prospective cohort of expected 3000 newborns, who will be recruiting in six maternity units of five Italian cities (Florence, Rome, Trieste, Turin and Viareggio) since October 2011. Mothers are contacted during pregnancy or at delivery and are offered to participate in the study. Upon acceptance, their newborns are recruited at birth and followed up until at least 18 years of age. At recruitment, the mothers donate a blood sample and complete a baseline questionnaire. Umbilical cord blood, pieces of umbilical cord and heel blood spots are also collected. Postnatal follow-up currently occurs at 6, 12, and 24 months of age using on-line or postal self administered questionnaire; further questionnaires and medical examinations are envisaged. Questionnaires collect information on several factors, including mother's and/or child's environmental exposures, anthropometric measures, reproductive factors, diet, supplements, medical history, cognitive development, mental health and socioeconomic factors. Health promotion materials are also offered to parents. DISCUSSION: Piccolipiù will broaden our understanding of the contribution of early-life factors to infant and child health and development. Several hypotheses on the developmental origins of health can be tested or piloted using the data collected from the Piccolipiù cohort. By pooling these data with those collected by other existing birth cohorts it will be possible to validate previous findings and to study rare exposures and outcomes.

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.

Evidence for a strong genetic influence on carotid plaque characteristics: an international twin study.

BACKGROUND AND PURPOSE: Few family studies reported moderate genetic impact on the presence and scores of carotid plaques. However, the heritability of carotid plaque characteristics remains still unclear. Twin studies more reliably estimate the relative contribution of genes to these traits in contrast to family study design. METHODS: One hundred ninety-two monozygotic and 83 dizygotic adult twin pairs (age 49±15 years) from Italy, Hungary, and the United States underwent B-mode and color Doppler ultrasound of bilateral common, internal, and external carotid arteries. RESULTS: Age-, sex-, and country-adjusted heritability was 78% for the presence of carotid plaque (95% CI, 55%-90%), 74% for plaque echogenicity (hypoechoic, hyperechoic, or mixed; 95% CI, 38%-87%), 69% for plaque size (area in mm2 in longitudinal plane; 50 percentile; 95% CI, 16%-86%), 74% for plaque sidedness (unilateral or bilateral; 95% CI, 25%-90%), 74% for plaque numerosity (95% CI, 26%-86%), 68% (95% CI, 40%-84%), and 66% (95% CI, 32%-90%) for the presence of plaque in carotid bulbs and proximal internal carotid arteries. No role of shared environmental factors was found. Unique environmental factors were responsible for the remaining variance (22%-34%). Controlling for relevant covariates did not change the results significantly. CONCLUSIONS: The heritability of ultrasound characteristics of carotid plaque is high. Unshared environmental effects account for a modest portion of the variance. Our findings should stimulate the search for genes responsible for these traits.

Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy.

The objective of this study was to determine, in an adolescent population, the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of NAFLD and cardiovascular risk factors with carotid artery intima-media thickness (IMT), a marker of subclinical atherosclerosis. The authors conducted a population-based study among 642 randomly selected adolescents aged 11-13 years in Reggio Calabria, southern Italy, between November 2007 and October 2008. Prevalences of overweight and obesity were 30.5% and 13.5%, respectively. The overall prevalence of NAFLD was 12.5%, increasing to 23.0% in overweight/obese adolescents. In univariate analysis, increased IMT was positively associated with the presence of NAFLD, body mass index (BMI), waist circumference, systolic blood pressure (all P's < 0.001), diastolic blood pressure (P = 0.006), gamma-glutamyl transpeptidase (P = 0.006), alanine aminotransferase (P = 0.007), and C-reactive protein (P = 0.008) and was inversely associated with high density lipoprotein cholesterol (P < 0.001). In multivariate analysis, NAFLD (P = 0.002), BMI (P = 0.004), waist circumference (P = 0.003), and systolic blood pressure (P = 0.005) retained significant associations. The authors conclude that NAFLD, BMI, waist circumference, and systolic blood pressure are independent markers of increased IMT in a random sample of adolescents.

Body mass index, cardiovascular risk factors, and carotid intima-media thickness in a pediatric population in southern Italy.

OBJECTIVES: Obesity and exposure to cardiovascular risk factors during adolescence may be associated with the development of atherosclerosis and cardiovascular diseases later in life. The objective of the study was to investigate whether any excess body weight, including moderate overweight, is associated with a more severe cardiovascular risk profile and signs of early atherosclerosis in a pediatric population. PATIENTS AND METHODS: A cross-sectional study was conducted among 646 adolescents ages 11 to 13 years from several primary schools of Reggio Calabria, Italy. Body mass index, waist circumference, blood pressure, glucose, insulin, homeostatic model assessment of insulin resistance, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and C-reactive protein (CRP) were determined. All of the subjects underwent carotid ultrasonography for the measurement of intima-media thickness. Complete clinical data were available from 575 subjects. RESULTS: Overweight was similarly frequent in boys and girls (31.2% vs 31.0%), whereas prevalence of obesity was higher in boys (18.4% vs 10.1%). Subjects with lower levels of HDL and higher levels of triglycerides, insulin, and CRP plasma were observed more frequently among overweight and obese subjects than nonoverweight. At multivariate analysis, HDL cholesterol, insulin, and CRP were associated (P < 0.05) with overweight and obesity in girls, whereas in boys, insulin and CRP were associated (P < 0.05) with overweight and obesity, and LDL cholesterol with obesity. The association between overweight or obesity and increased intima-media thickness, a sign of early atherosclerosis, was present in girls (P < 0.05) and was close to statistical significance in obese boys (P = 0.07). CONCLUSIONS: Overweight and obese adolescents have a higher prevalence of cardiovascular risk factors and show signs of early atherosclerosis. In girls, in particular, overweight is sufficient to determine a more severe cardiovascular risk profile.

Energy Drink and Alcohol mixed Energy Drink use among high school adolescents: Association with risk taking behavior, social characteristics.

PURPOSE: The aims of the study were to: a) examine the prevalence of energy drink (ED) and alcohol mixed with energy drink (AmED) consumption; b) investigate the relationships between ED and AmED with alcohol, binge drinking and drugs accounting for at risk behaviors among a representative sample of Italian adolescents. METHODS: A representative sample of 30,588 Italian high school students, aged 15-19years, was studied. Binary and multivariate logistic regression analyses were performed to determine the independent association of the potential predictors' characteristics with the ED and AmED drinking during the last year. RESULTS: Respectively 41.4% and 23.2% of respondents reported drinking EDs and AmEDs in the last year. Multivariate analysis revealed that consumption of EDs and AmEDs during the last year were significantly associated with daily smoking, binge drinking, use of cannabis and other psychotropic drugs. Among life habits and risky behaviors the following were positively associated: going out with friends for fun, participating in sports, experiencing physical fights/accidents or injury, engaging in sexual intercourse without protection and being involved in accidents while driving. CONCLUSIONS: This study demonstrates the popularity of ED and AmED consumption among the Italian school population aged 15-19years old: 4 out of 10 students consumed EDs in the last year and 2 out of 10 AmED. Multivariate analysis highlighted the association with illicit drug consumption and harming behaviors, confirming that consumption of EDs and AmEDs is a compelling issue especially during adolescence, as it can effect health as well as risk taking behaviors.

High prevalence of hepatitis B virus infection in B-cell non-Hodgkin's lymphoma.

In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.

The Italian Twin Register: new cohorts and tools, current projects and future perspectives of a developing resource.

Since its start as a database of "possible twins", the Italian Twin Register has developed remarkably in terms of twin approach and recruitment, data-management tools, the cohorts enrolled, and the breadth of information gathered, making the Italian Twin Register a valuable resource for genetic epidemiological research. The Italian Twin Register is a random population of twins at both the national level and within targeted geographical areas or birth cohorts. Further, the Register is linked with disease records and has recently implemented a web-based method for volunteer twin recruitment specifically designed to promote the Register and to disseminate information on genetic epidemiology. To date, approximately 9000 twins have joined the Italian Twin Register, the majority of whom (approximately 70%) represent young adults aged 20 at time of enrollment. Although the total number of twins recruited to date is far below the expected figure initially predicted, the newly established standardized procedures guarantee an increase of around 2000 twins each year. Following the collaboration between the Italian Twin Register and the main Italian nonprofit association for blood donors, twin DNA sampling and storage has recently accelerated contributing to the large amount of phenotypic data collected. The Italian Twin Register is currently involved in both population and clinical based studies on various complex phenotypes and diseases, some conducted within large European consortia.

Assessment of reference values for selected elements in a healthy urban population.

Reference values for 26 elements, namely Al, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn, Mo, Ni, Pb, Sb, Si, Sn, Sr, Tl, V, W, Zn and Zr are proposed in serum and blood of 110 healthy adults of the urban area of Rome. They were included in the study on the basis of strict criteria of eligibility and exclusion. With the exception of Ba, Bi, Co, Cr, Ni, Sb, Sn Tl in serum, and Bi, Hg, Si, V and W in whole blood, experimental data for each all the other analytes were found to approach a normal distribution. The estimated 5-95% references ranges (in ng ml(-1)) were reported. For several elements the reference ranges observed overlapped information available in the literature. Gender, age, body mass index, smoking habits and alcohol consume were used as grouping variables. Mutual associations were observed for several elements, as follows: Be, Ca, Co, Cr, Cu, Li, Mo, Pb and Zn with sex; Ca, Pb and Si with age (< and > 45 years); Co, Cr, Mo, Sb and Tl with body mass index; Cd and Pb with smoking habit; Cr and Pb with alcohol consume.

Concentration of elements in serum of patients affected by multiple sclerosis with first demyelinating episode: a six-month longitudinal follow-up study.

Twenty-six chemical elements and oxidative status were determined in serum of 12 patients with first demyelinating episode and brain magnetic resonance imaging compatible with the disease at different time points. Quantifications of Al, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn, Mo, Ni, Pb, Sb, Si, Sn, Sr, V, Tl, W, Zn and Zr, as well as of serum oxidative status and antioxidant capacity were carried out. The results were compared with values obtained from healthy subjects living in the same geographic area. Concentration variability, expressed as coefficient of variation (CV), was evaluated over a six months longitudinal follow-up. The CV was higher for Li and Pb, while showed minimal variation for Ca, Cu, Mg and Zn--elements strictly body regulated. Significant difference (p < or = 0.05) in mean concentrations of Ba, Ca, Cd, Cr, Li, Mn, Mo, Ni, Sb, Si, Sn and Zr between patients at time 0 and controls was also found.

Prevalence of hepatitis C virus infection in lymphoproliferative diseases other than B-cell non-Hodgkin's lymphoma, and in myeloproliferative diseases: an Italian Multi-Center case-control study.

BACKGROUND AND OBJECTIVES: Infection with hepatitis C virus (HCV) is associated with type II mixed cryoglobulinemia (MC), a lymphoproliferative disorder which, in some patients, evolves into overt B-cell non-Hodgkin's lymphoma (B-NHL). Recently, also the association between HCV infection and B-NHL, which had long been controversial, was confirmed in a large case-control study. Little knowledge is, however, available on possible associations between HCV infection and other lymphoid or myeloid malignancies. The present study was set up in order to investigate this aspect. DESIGN AND METHODS: The study was conducted in hematology departments of ten hospitals in different Italian cities. The cases consisted of consecutive patients with a new diagnosis of T-NHL, Hodgkin's disease (HD), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), multiple myeloma (MM), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). The controls were patients in other departments of the same hospitals. HCV infection was investigated by testing for HCV antibodies and HCV-RNA in serum samples. RESULTS: The prevalence of HCV infection was not higher in patients with HD (3.2%, 5 out of 157 cases) or MM (4.7%, 5 out of 107) than in controls. On the other hand, it was consistently higher in T-NHL (13.8%, 4 out of 30), CLL (9.0%, 9 out of 100), ALL (7.6%, 5 out of 54), AML (7.9%, 11 out of 140), and CML (12.2%, 6 out of 49) patients. These patient groups were not, however, large enough to render statistically significant results. INTERPRETATION AND CONCLUSIONS: Our data suggest that HCV infection may be associated not only with B-NHL but also with some other lymphoid and myeloid malignancies.

[Regression methods and causal inference: structural equations models]. / Metodi di regressione e inferenza causale: i modelli di equazioni strutturali.

The estimate of correlations among observed outcomes is crucial in biomedical research, especially when the aim of the study is to infer, from the magnitude of these correlations, the causal influence of certain, sometimes latent, factors. In such situations, a typical regression approach, known as "structural equation models" (SEM), which was introduced in the 1970s, becomes significant. These models allow hypotheses to be formulated quite clearly, thanks to some explicit and rigorous graphical representations, on which the "path analysis" is based. SEM, which were initially used in economics, have in the past decade been applied in a wide variety of fields, especially in genetic epidemiology. It's in this field that SEM are extraordinarily effective, representing a simple yet powerful means of estimating the contribution of genes and the environment to the phenotypic expression of a given disease. To this end, data on twins are particularly useful, and in this case the correlation between the outcomes describes the extent of similarity of the twin phenotypes. From this standpoint, SEM undoubtedly constitute one of the most promising statistical tools for family studies and quantitative genetic research. The method can be easily extended to traditional epidemiology, and some interesting applications have already been developed in occupational and social epidemiology. In this paper, we describe in detail the SEM approach and discuss the use of these models in genetic epidemiology, using twin studies as an example. We also discuss the application of SEM in fields other than genetic research.

[Twins in biomedical research and the creation of the "National Twin Registry"]. / I gemelli nella ricerca biomedica e l'istituzione del "Registro Nazionale Gemelli".

Twins are a valuable resource for the study of complex traits. The twin method is substantially based on the comparison between correlations and concordance in monozygotic (MZ) and dizygotic (DZ) twins and allows several applications in biomedical and molecular genetic research. It allows either the qualitative and quantitative evaluation of the influences that genetic and environmental factors exert on phenotypes or the estimation of trait variability. Moreover, classical genetic linkage analysis is more powerful if performed in DZ twins. However, the twin method has some pitfalls, such as the necessity that collected samples be representative of both twin and general population. For this reason, over the last few years, a number of Countries have established population-based twin registers, which guarantee the maximum level of representation and, consequently, are of extreme value for epidemiological studies. Italy is also implementing a national twin register. The following is the description of the procedure that led to the establishment of the Italian Twin Registry.

Bioimpedance analysis of body composition in an international twin cohort.

OBJECTIVE: Multiple twin studies have demonstrated the heritability of anthropometric and metabolic traits. However, assessment of body composition parameters by bioimpedance analysis (BIA) has not been routinely performed in this setting. DESIGN: A cross-sectional study. SETTING: Study subjects were recruited and assessed at twin festivals or at major university hospitals in Italy, Hungary, and the United States to estimate the influence of genetic and environmental components on body composition parameters in a large, wide age range, international twin cohort by using bioelectrical impedance analysis. SUBJECTS: 380 adult twin pairs (230 monozygotic and 150 dizygotic pairs; male:female ratio, 68:32; age years 49.1 ± 15.4; mean ± standard deviation; age range 18-82) were included in the analysis. RESULTS: Heritability was calculated for weight (82%; 95% confidence interval [CI]: 78-85), waist and hip circumferences (74%; 95%CI: 68-79), body fat percentage (74%; 95%CI: 69-79), fat-free mass (74%; 95%CI: 69-79) and body mass index (79%; 95%CI: 74-83). The completely environmental model showed no impact of shared environmental effects on the variance, while unshared environmental effects were estimated as between 18% and 26%. CONCLUSIONS: BIA findings provide additional evidence to the heritability of anthropometric attributes related to obesity and indicate the practical value of this simple method in supporting efforts to prevent obesity-related adverse health events.

Informing women on menopause and hormone therapy: Know The Menopause a multidisciplinary project involving local healthcare system.

BACKGROUND: Hormone therapy (HT) in the menopause is still a tricky question among healthcare providers, women and mass media. Informing women about hormone replacement therapy was a Consensus Conference (CC) organized in 2008: the project Know the Menopause has been launched to shift out the results to women and healthcare providers and to assess the impact of the cc's statement. METHODS: And Findings: The project, aimed at women aged 45-60 years, was developed in four Italian Regions: Lombardy, Tuscany, Lazio, Sicily, each with one Local Health Unit (LHU) as "intervention" and one as "control". Activities performed were: survey on the press; training courses for health professionals; educational materials for target populations; survey aimed at women, general practitioners (GPs), and gynaecologists; data analysis on HT drugs' prescription. Local activities were: training courses; public meetings; dissemination on mass media. About 3,700 health professionals were contacted and 1,800 participated in the project. About 146,500 printed leaflets on menopause were distributed to facilitate the dialogue among women and health care professionals. Training courses and educational cascade-process activities: participation ranged 25- 72% of GPs, 17-71% of gynaecologists, 14-78% of pharmacists, 34-85% of midwives. SURVEY: 1,281 women interviewed. More than 90% believed menopause was a normal phase in life. More than half did not receive information about menopause and therapies. HT prescription analysis: prevalence fell from 6% to 4% in five years. No differences in time trends before-after the intervention. Major limitations are: organizational difficulties met by LHU, too short time for some local activities. CONCLUSIONS: A huge amount of information was spread through health professionals and women. The issue of menopause was also used to discuss women's wellbeing. This project offered an opportunity to launch a multidisciplinary, multimodal approach to menopause looking not only at pharmacological aspects, but also at quality of life and information.

How to classify the oldest old according to their health status: a study on 1160 subjects belonging to 552 90+ Italian sib-ships characterized by familial longevity recruited within the GEHA EU Project.

The health status of the oldest old, the fastest increasing population segment worldwide, progressively becomes more heterogeneous, and this peculiarity represents a major obstacle to their classification. We compared the effectiveness of four previously proposed criteria (Franceschi et al., 2000; Evert et al., 2003; Gondo et al., 2006; Andersen-Ranberg et al., 2001) in 1160 phenotypically fully characterized Italian siblings of 90 years of age and older (90+, mean age: 93 years; age range: 90-106 years) belonging to 552 sib-ships, recruited in Northern, Central and Southern Italy within the EU-funded project GEHA, followed for a six-year-survival. Main findings were: (i) "healthy" subjects varied within a large range, i.e. 5.2% (Gondo), 8.7% (Evert), 17.7% (Franceschi), and 28.5% (Andersen-Ranberg); (ii) Central Italy subjects showed better health than those from Northern and Southern Italy; (iii) mortality risk was correlated with health status independently of geographical areas; and (iv) 90+ males, although fewer in number, were healthier than females, but with no survival advantage. In conclusion, we identified a modified version of Andersen-Ranberg criteria, based on the concomitant assessment of two basic domains (cognitive, SMMSE; physical, ADL), called "Simple Model of Functional Status" (SMFS), as the most effective proxy to distinguish healthy from not-healthy subjects. This model showed that health status was correlated within sib-ships, suggesting a familial/genetic component.

Genetic and environmental factors on the relation of lung function and arterial stiffness.

BACKGROUND: An association between reduced lung function and increased cardiovascular risk has been reported, but the underlying mechanisms are unknown. The aim of this study was to assess the heritability of lung function and to estimate its genetic association with arterial stiffness. METHODS: 150 monozygotic and 42 dizygotic healthy Hungarian and American Caucasian twin pairs (age 43 ± 17 years) underwent spirometry (forced vital capacity/FVC/, forced expiratory volume in 1 s/FEV1/; MIR Minispir, USA); and their brachial and central augmentation indices (AIx), and aortic pulse wave velocity (PWV) were measured by oscillometric Arteriograph (TensioMed Ltd, Budapest, Hungary). Phenotypic correlations and bivariate Cholesky decomposition models were applied. RESULTS: Age-, sex-, country- and smoking-adjusted heritability of FEV1, percent predicted FEV1, FVC and percent predicted FVC were 73% (95% confidence interval /CI/: 45-85%), 28% (95% CI: 0-67%), 68% (95% CI: 20-81%) and 45% (95% CI: 0-66%), respectively. Measured and percent predicted FVC and FEV1 values showed no significant phenotypic correlations with AIx or aortic PWV, except for phenotypic twin correlations between measured FEV1, FVC with brachial or aortic augmentation indices which ranged between -0.12 and -0.17. No genetic covariance between lung function and arterial stiffness was found. CONCLUSIONS: Lung function is heritable and the measured FVC and FEV are phenotypically, but not genetically, associated with augmentation index, a measure of wave reflection. This relationship may in turn reveal further associations leading to a better mechanistic understanding of vascular changes in various airway diseases.

Genetic and environmental effects on carotid flow velocities: an international twin study.

INTRODUCTION: Altered carotid blood flow velocities (CFV) have a complex background but the underlying genetic contribution is still unclear. We sought to evaluate the influence of genetics, shared and unshared environmental components on individual differences of CFV. METHODS: 193 healthy twin pairs, 126 monozygotic (MZ) and 67 dizygotic (DZ) (mean age 53 ± 14 years) recruited in Italy, in the United States and in Hungary underwent bilateral color-coded Doppler flow assessment of the common carotid artery (CCA) and of the internal carotid artery (ICA) in order to assess the peak systolic (PSV) and end diastolic (EDV) velocities. Means of bilateral CFV values were used in the analysis. RESULTS: Age- and country-adjusted intra-class correlations were higher in monozygotic than in dizygotic pairs for mean PSV of the ICA indicating a heritability of 63%. Unique environmental factors contributed to 37% of ICA PSV. With regards to the mean PSV and EDV of the CCA, and EDV of the ICA, heritability analysis indicated no discernible role for genetic components, while the contributions of shared and unshared environmental factors ranged between 56% and 63%, and between 37% and 44% adjusted for age and country, respectively. Mean ICA/CCA ratio was driven by unique environmental factors (82%) with modest heritability (18%). CONCLUSIONS: Our study showed that the heritability of ICA PSV and ICA/CCA ratio is moderate, while the findings do not support heritability of other investigated CFV values. Environmental effects account for a moderate to major portion of the variance. These findings support the value of early ultrasound screening as well as the prevention of modifiable environmental factors in case of altered carotid flow velocities.

Genetic and environmental components of neonatal weight gain in preterm infants.

BACKGROUND AND OBJECTIVES: Postnatal nutrition and subsequent weight gain or failure in the neonatal period are likely regulated by both the environment and the genetic background. With the goal of estimating the variability of postnatal weight gain due to genes and environment, comparison between monozygotic (ie, genetically identical) and dizygotic (genetically similar as 2 siblings) twins can be performed. METHODS: This study selected a very homogenous set of monozygotic and dizygotic twins who met the following inclusion criteria: gestational age between 30 and 36 weeks, birth weight between 1250 and 2200 g, and length of stay >12 days. Opposite-gender pairs and pairs that differed >20% in terms of birth weight were excluded from this analysis. The outcome measure of this study was the daily weight gain expressed in grams per kilogram per day during the period between day of birth and day of discharge. The average difference between members of a pair was computed in the 2 groups of twins, and heritability was estimated. RESULTS: The within-pair differences of the outcome measure were lower for monozygotic twins than for dizygotic twins, suggesting a strong genetic component. The total variance of the phenotype under study is explained by 2 sources of variation, additive genetic (87% [95% confidence interval: 67% to 94%]) and unique environment (13% [95% confidence interval: 6% to 33%]) components. CONCLUSIONS: This high heritability estimate could suggest using this set of criteria to identify genes that regulate postnatal weight gain or failure.