Inflammation is related to coronary flow reserve detected by positron emission tomography in asymptomatic male twins.

OBJECTIVES: This study sought to examine the relationship between inflammation and coronary microvascular function in asymptomatic individuals using positron emission tomography (PET) and assessment of coronary flow reserve (CFR). BACKGROUND: Coronary microvascular dysfunction is an early precursor of coronary artery disease (CAD) thought to result from endothelial cell activation and inflammation, but data are limited. METHODS: We examined 268 asymptomatic male monozygotic and dizygotic twins. Plasma biomarkers of inflammation and endothelial cell activation included C-reactive protein (CRP), interleukin (IL)-6, white blood cell count (WBC), vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1. Blood flow quantitation was obtained with [¹³N] ammonia PET at rest and after adenosine stress. CFR was measured as the ratio of maximum flow to baseline flow at rest; abnormal CFR was defined as a ratio < 2.5. A summed stress score for visible perfusion defects was calculated. RESULTS: In within-pair analyses, all biomarkers, except VCAM-1, were higher in twins with lower CFR than their brothers with higher CFR (p < 0.05). This was observed in the entire sample, as well as within pairs discordant for a CFR of <2.5. Associations persisted after adjusting for summed stress score and CAD risk factors. In contrast no biomarker, except IL-6, was related to the summed stress score of visible defects. CONCLUSIONS: Even in asymptomatic subjects, a decrease in coronary microvascular function is accompanied by a systemic inflammatory response, independent of CAD risk factors. Our results, using a controlled twin design, highlight the importance of coronary microvascular function in the early phases of CAD.

Leisure-time physical activity and nutrition: a twin study.

OBJECTIVE: To determine the association between long-term leisure-time physical activity/inactivity and eating behaviours in twin pairs discordant for physical activity for 30 years. DESIGN: Co-twin control design with cross-sectional data collection using questionnaire on eating habits and 5 d food diary. Differences in eating behaviours between physically active and inactive co-twins were analysed with pairwise tests. SETTING: Finland. SUBJECTS: Sixteen same-sex twin pairs (seven monozygotic and nine dizygotic, mean age 60 years) discordant for physical activity, selected from the Finnish Twin Cohort on the basis of physical activity discordance for 30 years, blinded to their possible differences in eating behaviours. RESULTS: The eating habits questionnaire revealed that physically active co-twins more frequently reported that it is easy to eat according to need, whereas overeating and/or restrictive eating was more common among the inactive co-twins (P = 0·035). Avoiding calories was more common among the active than inactive co-twins (P = 0·034). Based on food diaries the physically active co-twins had daily energy intake on average 15·5 kJ/kg higher than their inactive co-twins (P = 0·030). The active co-twins also had a higher intake of vitamin C (P = 0·004), total water (P = 0·044), legumes and nuts (P = 0·015) and sweets (P = 0·036), as well as a lower energy-adjusted intake of meat (P = 0·013). CONCLUSIONS: The physically active persons seem to eat more but not necessarily healthier food. However, habitual physical activity may help in eating according to need and in reaching and maintaining a healthy body composition. Therefore, it is necessary to incorporate both dietary and physical activity advice into health counselling.

Determinants of infant growth in four age windows: a twin study.

OBJECTIVE: To identify determinants of growth during infancy. STUDY DESIGN: The sample included 424 twin pairs from the East Flanders Prospective Twin Survey. Multilevel regression analysis was performed and intrapair growth correlations were calculated. The main outcome measure was growth, measured in g/kg/d (0-1 month) or in change in weight z-score (0-6, 6-12 and 12-24 months). RESULTS: Growth during infancy was associated with birth weight and gestational age. One z-score increase in birth weight resulted in -1.77 g/kg/d less growth from 0-1 month (P < .0001). The effect size decreased with age until -0.02 (P = .70) z-scores less growth from 12 to 24 months. Corresponding numbers for one z-score increase in gestational age decreased from 0.78 (P = .001) to 0.06 (P = .40). From 12 to 24 months, paternal height had a significant positive effect. The difference in growth similarity within the twin pair between monozygotic and dizygotic twins increased from non-significant from 0 to 1 month (P = .49) to a monozygotic:dizygotic ratio approximating 2:1 from 12 to 24 months (P = .002). CONCLUSION: From 0 to 1 month, environmental factors are most important for growth, whereas genetic factors become more important over time. This is a first step in identifying age windows for future counseling and interventions on the effects of accelerated growth.

Birth weight discordance of twin pairs and their subsequent growth patterns.

BACKGROUND: Few studies have compared the growth of a twin with its co-twin and particularly in relation to birth weight discordance. AIM: The study investigated how the degree of birth weight discordance affected subsequent growth. METHODS: Birth weight discordance of 762 twin pairs was determined. Subsequent weight, height and occipital-frontal head circumference (OFC) measurements were obtained between the ages of 2-9 years. Corresponding standard deviations scores (SDS) were analysed according to birth weight discordance, sex and zygosity. Weight status was taken into account by assigning twins into sub-groups according to whether they were the heavier twin at birth and remained heavier, became the lighter of the twin pair or had the same weight, for subsequent measurements. RESULTS AND CONCLUSIONS: The degree of birth weight discordance had little effect on subsequent growth except in monozygotic (MZ) twins with >20% discordance. Severe low birth weight ( < 1.95 kg) is more significant in suppressing subsequent growth than the degree of discordance per se. A surprisingly high proportion of twins reversed their weight status when reviewed at an older age.

Genetic and environmental influences on blood pressure and body mass index in Han Chinese: a twin study.

The familial aggregation of blood pressure (BP) may be partly due to the familial aggregation of obesity, caused by genetic and/or environmental factors that influence both. Gene-obesity interactions are expected to result in different heritability estimates for BP at different obesity levels. However, the latter hypothesis has never been tested. The present study included 1243 monozygotic and 833 dizygotic Han Chinese twins (mean±s.d. age: 37.81 ± 9.82; range: 19.1-81.4) from the Chinese National Twin Registry. Body mass index (BMI) was used as the index of general obesity. The outcome measures were systolic BP (SBP) and diastolic BP (DBP). Quantitative genetic modeling was performed using Mx software. The SBP and DBP heritabilities were 46 and 30%, respectively. The positive correlations of BMI with SBP (r=0.26) and with DBP (r=0.27) were largely due to genetic factors (approximately 85%). Genetic factors, which also influence BMI, account for 6 and 7% of the total variance for SBP and DBP, respectively. The gene-obesity interaction analysis showed that both common and unique environmental influences on SBP increased with increasing levels of BMI, resulting in a lower heritability at higher BMI levels, whereas for DBP the heritability remained unchanged at higher BMI levels. Our results suggest that higher BMIs may reduce SBP heritability through a larger impact of environmental effects. These conclusions may be valuable for gene-finding studies.

An investigation into the relationship between soft tissue body composition and bone mineral density in a young adult twin sample.

The purpose of this study was to investigate the relationship of fat mass (FM) and lean mass (LM) with bone mineral density (BMD) independent of genetic effects. We also assessed the extent to which genetic and environmental influences explain the associations between these phenotypes. Body composition and BMD were measured using dual-energy X-ray absorptiometry in 57 monozygotic and 92 same-sex dizygotic twin pairs, aged 23 to 31 years, chosen to represent a wide range of intrapair differences in body mass index (BMI; 0 to 15.2 kg/m(2)). Heritability estimates were adjusted for height and gender. In multiple linear regression analysis, intrapair differences in both FM and LM were independently associated with intrapair differences in BMD at most skeletal sites after adjustment for gender and differences in height. Within monozygotic and dizygotic pairs, LM was a significantly stronger predictor of whole-body BMD than FM (p < .01). Additive genetic factors explained 87% [95% confidence interval (CI) 80%-91%), 81% (95% CI 70%-88%), and 61% (95% CI 41%-75%) of the variation in whole-body BMD, LM, and FM, respectively. Additive genetic factors also accounted for 69% to 88% of the covariance between LM and BMD and for 42% to 72% of the covariance between FM and BMD depending on the skeletal site. The genetic correlation between LM and whole-body BMD (r(g) = 0.46, 95% CI 0.32-0.58) was greater than that of FM and whole-body BMD (r(g) = 0.25, 95% CI 0.05-0.42). In conclusion, our data indicate that peak BMD is influenced by acquired body weight as well as genetic factors. In young adulthood, LM and BMD may have more genes in common than do FM and BMD.

Spontaneous reduction before 12 weeks' gestation and selective reduction similarly extend time to delivery in in vitro fertilization of trichorionic-triamniotic triplets.

OBJECTIVE: To determine the prevalence and the relative benefits conferred by selective and spontaneous reduction of one or more fetuses in trichorionic triamniotic triplet pregnancies on time to delivery. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): IVF patients with trichorionic triamniotic triplets between January 1998 and December 2007. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gestational length at time of delivery. RESULT(S): Selective reduction to twins was used in 87 of the 153 (56.9%) triplet pregnancies that did not spontaneously reduce prior to <12 weeks, and was associated with longer gestation (13.9 days) with a fourfold greater likelihood of delivery at ≥ 34 weeks' gestation (odds ratio [OR], 4.3; 95% confidence interval [CI] = 2.2-8.6), compared with pregnancies not undergoing selective reduction. Compared with ongoing triplets, spontaneous reduction at <12 weeks' gestation (28 cases) was associated with longer gestation (13.7 days) and significantly greater likelihood delivering at or after 34 weeks' gestation (OR, 3.7; 95% CI, 1.4-9.9). CONCLUSION(S): Selective reduction of one fetus was used in 56.9% of patients in this population. Early spontaneous reduction (<12 weeks) and selective reduction to twins each conferred similar benefits by extending time to delivery and increasing the likelihood of delivery at or after 34 weeks' gestation.

Middle cerebral artery-peak systolic velocity in dizygotic twins with anti-E alloimmunization.

Middle cerebral artery-peak systolic velocity (MCA-PSV) has been reported to predict fetal anemia with similar accuracy as amniotic ΔOD450 assay. Alloimmunized dizygotic twin pregnancy allows us to compare anemic and non-anemic twins in the same intrauterine environment. We herein present a case of Rh (E)-incompatible dizygotic twin pregnancy, where MCA-PSV could precisely detect the anemia in one of the twins. A 36-year-old woman, whose previous child required exchange transfusion due to hemolytic anemia of newborn (HFDN), conceived twins after in vitro fertilization-embryo transfer. At 24 weeks' gestation, MCA-PSV of twin A and twin B were 23.9 cm/s (0.8 multiples of median; MoM) and 30.7 cm/s (1.0 MoM), respectively. At 31 weeks' gestation, MCA-PSV values of both twins were sharply elevated to nearly 1.4 MoM. Thereafter, MCA-PSV of twin A fell to 1.0 MoM, whereas MCA-PSV of twin B exceeded 1.5 MoM at 34 weeks' gestation. Development of fetal anemia was suspected and emergency cesarean section was performed. Twin B showed moderate anemia with positive direct Coombs' test and was diagnosed as HFDN due to anti-E alloimmunization. Twin B required phototherapy and red cell transfusion, but exchange transfusion was safely obviated.

Primary tooth emergence in Australian children: timing, sequence and patterns of asymmetry.

BACKGROUND: Information on the timing and sequence of human tooth emergence is valuable when analysing human growth and development, predicting the age of individuals, and for understanding the effects of genetic and environmental influences on growth processes. This paper provides updated data on the timing and sequence of primary tooth emergence in Australian children for both clinicians and researchers. METHODS: Twins were recruited from around Australia with data collected through parental recording of twins' primary tooth emergence. One twin from each pair was then randomly selected to enable the calculation of descriptive statistics for timing, sequence and asymmetry in tooth emergence. RESULTS: The first and last primary teeth emerged, on average, at 8.6 months and 27.9 months, respectively, with teeth emerging in the order: central incisor, lateral incisor, first molar, canine, second molar. Left-side antimeric teeth were more likely to emerge before their right-side counterparts but this was not statistically significant. At least 35% of all antimeric pairs had emerged within two weeks of each other, serving as a useful guideline for assessing symmetrical versus asymmetrical development. CONCLUSIONS: Primary tooth emergence in Australian twins is occurring later than reported previously for Australian singletons but is consistent with findings for singletons in other ethnic groups. The most common sequence of primary tooth emergence appears to be consistent in twins and singletons and has not changed over time.

A longitudinal study on genetic and environmental influences on leisure time physical activity in the Finnish Twin Cohort.

The purpose of this study was to examine changes in the contribution of genetic and environmental influences to leisure time physical activity among male and female twins over a 6-year follow-up. At baseline the sample comprised 4,280 monozygotic and 9,276 dizygotic twin individuals, and at follow-up 4,383 monozygotic and 9,439 dizygotic twin individuals. Participants were aged 18-54 years at baseline. Genetic modeling results showed that genetic influences on leisure time physical activity declined from baseline (44%) to follow-up (34%). Most of the genetic influences identified at baseline were present at followup (r(g) = 0.72). Specific environmental influences increased from baseline (56%) to follow-up (66%) while at follow-up new environmental time-specific influences were observed (r(e) = 0.23). The model with sex differences showed a higher estimate of genetic influences for men than women both at baseline (men 47% vs. women 42%) and at follow-up (men 38% vs. women 31%). The additive genetic correlation for this phenotype was greater for men (r(g) = 0.79) than women (r(g) = 0.64). The specific environmental influences were corresponding; at baseline men 53% and women 56% and at follow-up men 62 % and women 69%. The environmental correlations between the two time points were similar for men (r(e)= 0.21) and for women (r(e)= 0.24). In conclusion, in a sample of healthy twins most of the genetic influences on leisure time physical activity expressed at baseline were present at 6 years of follow-up. New specific environmental factors underlying follow-up leisure time physical activity were observed.

Monozygotic twins are discordant for chronic periodontitis: clinical and bacteriological findings.

OBJECTIVES: The aim of this study was to assess, in monozygotic (MZ) and dizygotic (DZ) twin pairs in whom the proband of the twin pair was suffering from moderate to severe chronic periodontitis, the contribution of genetics, periodontal pathogens and lifestyle factors towards the clinical phenotype. MATERIAL AND METHODS: For this study, 18 adult twin pairs were selected on the basis of interproximal attachment loss (AL) >or=5 mm in >or=2 non-adjacent teeth in one twin member. The study included 10 MZ and eight DZ twin pairs, in whom the periodontal condition, presence of periodontal pathogens, educational level, smoking behaviour and body mass index (BMI) were evaluated. RESULTS: Both MZ and DZ twins were discordant regarding AL and alveolar bone loss. Discordance was greater in DZ compared with MZ twins. In MZ twins, the discordance could not be explained by education, smoking, BMI and periodontal pathogens. In DZ twins, 45.6% of the discordance could be explained by more pack-years of the probands. CONCLUSION: The results confirm a possible role of genetic factors in periodontitis. However, the magnitude of the genetic effects on disease severity may have been overestimated previously.

Physical features observation: is it repeatable in zygosity determination of Chinese adult twins?

This study reports on the inter- and intrarater reliability of physical features observation. Study subjects were 176 Chinese adult persons, consisting of 89 males and 87 females. Three trained research assistants responded simultaneously and respectively to 12 items regarding the subject's physical features including 'hair', 'Mongoloid folds', left and right 'ear lobes', 'earwax', 'nostril shape', 'tongue rolling', left and right 'hitchhiker's thumb', 'mid-digital hair' and left and right 'simian crease' at the moment of interview. And 14 days later, these subjects received the same observation once again. The results showed that the inter- and intra-observer agreements of 'hair', 'earwax', 'tongue rolling', 'mid-digital hair' and 'simian crease' were almost perfect with most kappa (kappa) coefficients >or= .80, while 'Mongoloid fold' and 'nostril shape' showed poor inter-observer agreement and 'nostril shape' showed poor intra-observer agreement (kappa < .40). Two other physical features, 'hitchhiker's thumb' and 'ear lobes' showed moderate inter-observer agreement and three features, 'hitchhiker's thumb', 'ear lobes' and 'Mongoloid fold', showed moderate intra-observer agreement (.40

Preliminary evidence that estradiol moderates genetic influences on disordered eating attitudes and behaviors during puberty.

BACKGROUND: Puberty moderates genetic influences on disordered eating attitudes and behaviors, with little genetic influence before puberty but large (50%) genetic effects during and after puberty. To date, however, nothing is known about the mechanisms that underlie these effects. Estradiol is a particularly promising candidate, as estrogens become elevated at puberty and regulate gene transcription within neurotransmitter systems important for eating-related phenotypes. The aim of this pilot study was to examine whether estradiol levels moderate genetic influences on disordered eating during puberty. METHOD: Participants included 198 female twins (ages 10-15 years) from the Michigan State University Twin Registry. Disordered eating attitudes and behaviors were assessed with the total score, weight preoccupation, body dissatisfaction and binge eating/compensatory behavior subscales of the Minnesota Eating Behavior Survey (MEBS). Afternoon saliva samples were assayed for estradiol levels. Moderation of genetic effects was examined by comparing twin correlations in low versus high estradiol groups. RESULTS: In the low estradiol group, monozygotic (MZ) and dizygotic (DZ) twin correlations for all MEBS scales were similar, suggesting little genetic influence. In the high estradiol group, the MZ twin correlation was more than double the DZ twin correlation, indicating the presence of genetic effects. Findings could not be accounted for by age, body mass index or the physical changes of puberty. CONCLUSIONS: Estradiol may be one important moderator of genetic effects on disordered eating during puberty. Larger twin studies are needed to replicate this pilot work and quantify the extent of genetic moderation.

Inheritance of 18 quantitative dermatoglyphic traits based on factors in MZ and DZ twins.

18 quantitative finger and palmar dermatoglyphic traits were analyzed with the aim of determining genetic effects and common familial environmental influences on a large (358 nuclear pedigrees) number of twins (MZ and DZ). Genetic analysis based on principal factors includes variance and bivariate variance decomposition analysis. Especially, Factor 1 (digital pattern size) is remarkable, due to its degree of universality. The results of genetic analysis revealed all three extracted factors have significant proportion of additive genetic variance (93.5% to 72.9%). The main results of bivariate variance decomposition analysis appears significant correlation in residual variance between digital pattern size factor (Factor 1) versus finger pattern intensity factor (Factor 4), and palmar main lines factor (Factor 2) verses a-b ridge count (Factor 3), but there was no significant correlation in the genetic variance of factors.

How studies of twins can inform our understanding of dental morphology.

Two metaphors are presented to highlight concepts that could lead to a paradigm shift in dental studies of twins. The first, derived from the Song of Solomon in the Bible, refers to teeth as being twins. This viewpoint emphasises that each tooth should be viewed as a paired structure, not only with its antimere (within the same arch) but also with its isomer (in the opposing arch). The other metaphor provided by Waddington in 1957 is visual and involves 'an epigenetic landscape' that represents the processes of decision-making by cells during development. It likens the different stages of cellular decision-making to a ball rolling down an undulating landscape of interconnecting hills and valleys. This viewpoint helps to explain how distinct differences in dental phenotypes may arise both within and between monozygotic (MZ) co-twins due to relatively minor temporospatial effects during development. Measurements of maximum mesiodistal diameters of teeth in a pair of MZ twins, using calipers and also 2D and 3D imaging systems, have demonstrated that differences in dental crown size occur between antimeric pairs and between corresponding teeth of MZ co-twins. By defining new dental phenotypes that provide more comprehensive descriptions of tooth size and shape, and by drawing on the metaphors described, we are confident of providing new insights into the reasons for observed similarities and differences within, and between, the dentitions of twins. Our approaches will focus on multivariate analyses that take into account the paired arrangement of teeth and also explore epigenetic, as well as genetic and environmental, sources of variation.

Size of ovulatory follicles in cattle expressing multiple ovulations naturally and its influence on corpus luteum development and fertility.

Long-term genetic selection of cattle for fraternal twins has increased the frequency of twin and triplet ovulations. In contrast, the ratio of fetal numbers to ovulation sites in pregnant females with twin (0.83) or triplet (0.73) ovulations is <1.0 and the number of calves per parturition is 1.6 and 2.0, respectively. Failure of individual twin or triplet ovulations to yield a conceptus in fertile females indicates a significant contribution of ovulation or oocyte anomalies to increased fertilization failure or early embryonic mortality. The present objective was to identify physiological traits affecting conception in cyclic cattle expressing multiple ovulations naturally, including the effect of ovulation rate on follicle or corpus luteum (CL) size, and their relationship to conception. Diameter of the individual ovulatory follicles was measured by transrectal ultrasonography at AI and ranged from 8 to 30 mm, with a trend for diameter of the individual follicles, and associated CL, to decrease with increasing ovulation rate. Independent of ovulation rate, ovulatory follicles were smaller (P < 0.05) for nulliparous heifers (1.5 yr) compared with parous cows (> or =2.5 yr). Pregnancy and fetal status were diagnosed by transrectal ultrasonography between 42 and 72 d after AI. Fertility was reduced (P < 0.01) for small twin or triplet ovulatory follicles (8 to 8.9 mm vs. 10 to 17.9 mm diam.), whereas fertility in monovular females was reduced (P < 0.01) for large ovulatory follicles (> or =22 vs. 14 to 17.9 mm). Plasma progesterone concentrations increased with ovulation rate and were correlated positively with total CL or ovulatory follicle volume per female, indicating that CL size and function were influenced by the size of the follicle of origin. Progesterone was greater (P < 0.05) in the blood of nulliparous heifers compared with parous cows. The increased proportion of small ovulatory follicles associated with twin and triplet ovulations indicates that some ovulatory follicles were either selected to ovulate at a lesser stage of maturity or rescued while undergoing atresia, thus compromising oocyte competency or ovulation. Of greatest importance for reduced fertility was the greater incidence of pregnancy losses occurring in the middle of gestation in females gestating 2 or more fetuses as an apparent effect of uterine crowding, especially when 2 or more fetuses were contained within 1 uterine horn.

The nature of individual differences in EEG parameters during homogeneous visual field in 5- and 6-year-old twins: a pilot study.

OBJECTIVE: To assess the genetic and environmental influences on the inter-individual variability of spectral EEG parameters under two conditions of reduced visual input in preschoolers. METHODS: EEG was recorded in 21 monozygotic and 20 same-sex dizygotic twin pairs aged 5-6 years under the Closed eyes and Darkness conditions. The contributions of genetic and environmental influences to individual EEG parameters were estimated using structural equation modeling. RESULTS: The alpha rhythm parameters - both spectral amplitude and frequency - were influenced mainly by genetic factors. Theta spectral amplitude variance was presumably accounted for by both genetic and shared environmental factors. The difference in the nature of population variance between EEG alpha and theta band spectral amplitudes was reproduced for two identical functional loads: Closed eyes and Darkness. CONCLUSIONS: The majority of EEG spectral parameters in preschool children are determined by genetic factors. Tentative finding on systematic environmental influences on theta spectral amplitude under the condition of reduced visual input may point to the role of experience in the individual differences in the functioning of theta response system. SIGNIFICANCE: The findings contribute to the scanty knowledge about the heritability of EEG rhythms in preschool children.

Heritability of left ventricular and papillary muscle heart size: a twin study with cardiac magnetic resonance imaging.

AIMS: Earlier studies in monozygotic (MZ) and dizygotic (DZ) twins showed genetic variance on echocardiographically determined heart size. However, cardiovascular magnetic resonance (CMR) is more precise and reproducible. We performed a twin study relying on CMR, focusing on left ventricular (LV) mass and papillary muscle, since there are no genetic reports on this structure. METHODS AND RESULTS: We measured left heart dimensions of 25 healthy twin pairs with a 1.5T MR scanner, analysed with the mass, Medis Software. We performed heritability analysis and tests for genetic influences shared between cardiac structures. We found that CMR-based heritability estimates (h(2) = 84%) substantially exceeded estimates based on echocardiography. We also found significant genetic influence on papillary muscle mass (h(2) = 82%). Bivariate analysis of papillary and LV muscle mass revealed significant genetic influences shared by both phenotypes (genetic correlation 0.59) and suggested an additional genetic component specific to papillary muscle. We observed correlations between body mass index, surface area, and systolic blood pressure with cardiac dimensions, even in this small study. Environmental influences were relevant as well, indicating reciprocal influences on papillary vs. LV muscle mass. CONCLUSION: Cardiovascular magnetic resonance, even with few subjects, allows a genetic assessment of cardiac structures that cannot be attained with echocardiography. Hitherto fore unappreciated relationships can be uncovered by this method.