Heritability estimates for the constitutional levels of the collectins mannan-binding lectin and lung surfactant protein D. A study of unselected like-sexed mono- and dizygotic twins at the age of 6-9 years

The collectins mannan-binding lectin (MBL) and lung surfactant protein D (SP-D) play a significant role in innate immunity. Structural as wells as promoter variants are known for MBL and different alleles correlate with low MBL concentrations in serum and predispose to infectious diseases. Structural variants are also known for SP-D but these have not been linked to disease states. The aim of the present study was to provide heritability estimates for the constitutional levels of MBL and SP-D in children. A population of 26 monozygotic (MZ) and 36 dizygotic (DZ) like-sexed twin pairs aged 6-9 years was studied. Intraclass correlations were significantly higher in MZ than in DZ twins, indicating substantial genetic influence on both MBL and SP-D levels. Biometric model fitting showed that the estimated heritability was 0.96 (95% CI 0.92-0.97) for MBL with the presence of non-additive genetic factors and non-shared environmental factors and 0.91 (95% CI 0.83-0.95) for SP-D with additive genetic and non-shared environmental factors. The data indicate quantitatively very strong genetic dependence for the serum levels of both MBL and SP-D.     

Intra-pair similarity in IQ of monozygotic and dizygotic male twins at 12 and 18 years of age

Verbal and inductive test results have been collected for a group of male twins in grade 5 at 12 years of age and at enrolment to military service at 18 years of age. MZ twin pairs tend to get progressively more concordant for both verbal and inductive ability from age 12 to 18. DZ twins, on the other hand, get progressively more concordant for inductive ability, while they tend to get less concordant for verbal ability. The results are interpreted with reference to a model taking heredity-environment interaction into account. The discordant trend found when comparing intra-pair similarity in verbal ability for MZ and DZ twins thus seems to indicate the presence of interactional and correlational effects.

For inductive ability, however, the difference between within-pair correlations for MZ and DZ twins tends to be of the same magnitude at both 12 and 18 years of age. Probably this type of test is less differentially influenced by the environments being sampled, at least under present circumstances, when children are not specifically trained to solve the kind of items included in the inductive test.

Regression effects for the two tests and possible explanations to the increase from age 12 to 18 in both MZ and DZ within-pair similarity for inductive test scores are discussed.     

Intra-pair similarity in physical growth of monozygotic and of dizygotic twins during puberty

The growth of 323 pairs of twins (94 MZ pairs, 133 DZ like-sexed pairs and 97 DZ unlike-sexed pairs) born in 1954/55 was studied longitudinally from 10 to 18 years for boys and 10 to 16 years for girls. Within-pair comparisons for height and weight have been made for MZ twins and DZ like-sexed twins. A significantly higher concordance in height was found for MZ pairs than for DZ pairs during puberty, for both boys and girls. Yearly height increments were also more similar for the MZ pairs, showing that the height spurt occurs more simultaneously for MZ twins in comparison to DZ twins. Height seems to be a strongly genetically regulated variable.

The MZ twins also show a high concordance in weight during the whole investigation period. The DZ pairs, however, became progressively less similar in weight. This is most pronounced for the DZ girls, the intra-class correlation for weight decreasing from 0·66 at 10 years to 0·23 at 16 years. This could imply stronger interactional effects for girls than for boys with regard to weight during puberty.     

Genetic regulation of growth from birth to 18 years of age: The Swedish young male twins study

Growth is a complex process, and only little is known on the genetic regulation of it. We analyzed the effect of genetic and environmental factors on growth in a longitudinal Swedish cohort of 231 monozygotic and 144 dizygotic twin pairs born 1973–1979 with length or height measured annually from birth to age 18. The data were analyzed by two different multivariate variance component models for twin data using the Mx statistical package. At birth and 1 year of age, a substantial part of the variation in length was because of common environment (50 and 57%, respectively) and the effect of genetic factors was minor. After 2 years of age, 91–97% of the variation of height could be explained by genetic differences whereas the rest was because of environmental variation not shared by twins. The genetic correlation between heights at ages 2 and 18 was 0.73 (95% confidence intervals 0.68–0.77) showing that 53% of the genes affecting height at these ages are the same or closely linked; with increasing age the correlation with genetic effects at age 18 become subsequently stronger. Especially in mid‐childhood, growth was largely regulated by the same genetic factors. During puberty new genetic factors started to affect height, but also genetic variation affecting height at previous ages remained. These results suggest that genetic regulation of growth is rather uniform, which is encouraging for further efforts to identify genes affecting growth. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

The influence of genetic factors on the immune response as judged by pneumococcal vaccination of mono- and dizygotic Caucasian twins.

Eighty-four mono- and dizygotic Caucasian twins randomly chosen, except for age and sex distribution, were vaccinated with a 23-valent pneumococcal vaccine. Blood samples were drawn before and after vaccination and the concentration of IgG, IgG1 and IgG2 pneumococcal antibodies was measured using an ELISA technique which only detects type-specific capsular antibodies, since C-polysaccharide antibodies in serum were removed. A significantly closer correlation was found regarding mean IgG and IgG2 antibody concentrations after vaccination in mono- compared with dizygotic twins, and this correlation was seemingly type-specific. Since environmental factors in our study population should not contribute more to the immune response in one type of twins compared with the other, we conclude that genetic factors influence the IgG and IgG2 antibody response to pneumococcal vaccination, and that this influence seems to be type-dependent.     

Apparent influence of marker genotypes on variation in serum cholesterol in monozygotic twins

Ninety-seven monozygotic (MZ) twin pairs were grouped by marker system genotypes, and mean intrapair differences in serum total cholesterol level were compared between groups. Significant differences were found when the MNSs and the Kidd blood group systems were considered. The results appear to suggest a restrictive effect of certain normal marker genes on environmentally caused variation in serum cholesterol level.     

Histamine release from whole blood induced by anti-IgE: relationship to patient age, age at onset and serum IgE levels

Anti-IgE-induced histamine release from basophils was examined in 46 asthmatic subjects using a whole blood method. Basophils from subjects less than 30 years old released more histamine than those from subjects aged 41 to 50. The age at onset of the disease also affected the reactivity of basophils to anti-IgE: basophils showed a high response in subjects whose age at onset was between 0 and 10 years, and low response in the subjects whose age at onset was between 41 and 50 years. There was a correlation between histamine release and serum IgE levels. However, individual dose-response curves of histamine release varied greatly in whom serum IgE levels were low.     

Prolonged exclusive breastfeeding is associated with increased atopic dermatitis: a prospective follow-up study of unselected healthy newborns from birth to age 20 years

BACKGROUND: Exclusive breastfeeding for the first 6 months is recommended by the World Health Organization and considered allergy preventive. However, it is not known whether prolonging exclusive breastfeeding for over 6 months provides further benefit in allergy prevention. OBJECTIVE: The aim of this prospective 20-year follow-up study was to find out whether the allergy protective effect can be enhanced by prolonging strictly exclusive breastfeeding for > or =9 months of age. A total of 200 unselected healthy newborns were enrolled in the study. Their mothers were encouraged to maintain exclusive breastfeeding for as long as possible. The number of infants on strictly exclusive breastfeeding was 167 at 2, 116 at 6, 36 at 9 and 7 at 12 months of age. Of the 200 infants, 42% had a family history of allergy. The children were re-assessed at ages 5 (n=163), 11 (n=150) and 20 years (n=164) with clinical examination, skin prick testing, and parental and personal structured interviews. RESULTS: Exclusive breastfeeding prolonged for > or =9 months was associated with atopic dermatitis (P=0.002) and symptoms of food hypersensitivity (P=0.02) at age 5 years, and with symptoms of food hypersensitivity at age 11 years (P=0.01), in children with a family history of allergy. CONCLUSION: Prolonging strictly exclusive breastfeeding for > or =9 months was not helpful in atopy prevention, instead, it was associated with increased atopic dermatitis and food hypersensitivity symptoms in childhood.     

The growth, development and education of Finnish twins: a longitudinal follow-up study in a birth cohort from pregnancy to nineteen years of age

The growth, development and vocation of 289 twins in a one year birth cohort beginning during pregnancy and followed up to the age of 19 years was compared with that of 11,623 singletons and two sets of controls matched either by maternal factors only or by these and perinatal morbidity, all from the same cohort. The twins were more often pre-term and small for their gestational age, and had more often suffered from perinatal asphyxia, neonatal hyperbilirubinaemia and hypoglycemia. They had learned to walk without support later than the singletons and the controls matched only by maternal factors, but this difference did not exist between the twins and the controls also matched by perinatal morbidity. The same kind of result was found when studying the number of words spoken at the age of one year and physical growth at the ages of 1 and 14 years. The twins did not differ significantly from the singletons during their compulsory nine years of primary and secondary schooling. According to the national registers of vocational choices, the twins had applied for admission to further education courses less often than the singletons or their controls matched only by maternal factors, but not when compared with the controls also matched by perinatal morbidity. Logistic regression analysis revealed numerous perinatal or environmental factors having an adverse effect on educational achievements, but the twin situation itself was not shown to have adverse effects. About half of the same-sex twin pairs and one seventh of the opposite-sex pairs had chosen the same vocation, compared with just over 10% similarity between the twins and their controls.     

No genetic effect on variation in field dependence: A study of rod-and-frame scores in families of monozygotic twins

Rod-and-frame scores for 74 monozygotic (MZ) twin pairs and their spouses and children were analyzed, applying the MZ half-sib model [Nance, W. E., and Corey L. A., (1976). Genetics83:811–826] to estimate the relative importance of genetic and environmental effects. The results indicated no genetic effect and a large individual environmental effect (69% of the total variance). The environmental variance shared by the nuclear family members was 31% of the total variance. Of this common component, approximately two-thirds was shared by the members of the two families of cotwins, suggesting that families of monozygotic twins share many experiences or possibly influence each other reciprocally.The Norwegian Research Council for Science and Humanities provided financial support     

The neural correlates of verbal encoding and retrieval in monozygotic twins at low or high risk for depression and anxiety

Emotional processing and brain activation were examined during an encoding and recognition paradigm using emotionally salient words in a sample of monozygotic twin pairs at low or high risk for anxiety and depression. Discordant twin pairs were used to chart the effects of environmental risk factors and concordant twin pairs were used to chart the effects of genetic risk factors on performance and brain activation. Performance data did not support the existence of a negative response bias in subjects at high risk. At the neural level, however, increased left inferior frontal gyrus (LIFG) activation by negative words was found in high-risk subjects, most prominently during recognition. Increased LIFG activity was found in subjects at high risk through either genetic or environmental risk factors. These results suggest that fMRI activation of the LIFG in a verbal emotional memory task may be a useful vulnerability marker for anxiety and depression.     

Determinants of growth in body length from birth to 6 years of age: A longitudinal study of Lublin children

The effect of determinants of growth in body length from birth to 6 years of age were studied in a longitudinal sample of 59 male and 70 female infants from Lublin, Poland. Structural equation modeling (SEM) was used to study the effects of gender of the child, occupation of the parents, the educational level of the parents, per capita income, the stature of the parents, and the weight of the mother on body length at birth and at 1, 2, 3, and 6 years of age. Significant sex differences in length were observed at birth and during the first 2 years of postnatal life, but not in the period between 3 and 6 years of age. Socioeconomic status (SES), expressed as a latent variable in the SEM, was not related to body length at birth but was significantly related to body length during infancy and, to a lesser extent, to body length during childhood. Paternal stature was not related to body length at birth and during infancy, but was significantly related to body length from 3 years onwards. Maternal stature was significantly related to body length at birth and at 1 year of age, but not thereafter, while maternal weight was significantly related to body length at birth only. © 1996 Wiley-Liss, Inc.     

Levocetirizine: pharmacokinetics and pharmacodynamics in children age 6 to 11 years

BACKGROUND: The pharmacokinetics and pharmacodynamics of medications may differ between children and adults, necessitating different dose regimens for different age groups. Levocetirizine, the active enantiomer of cetirizine, is used in the treatment of allergic rhinitis and chronic urticaria in Europe. Its pharmacokinetics and pharmacodynamics have not yet been studied prospectively in school-age children. OBJECTIVES: This study was performed to investigate levocetirizine pharmacokinetic disposition and pharmacodynamics in relation to skin reactivity to histamine in children aged 6 to 11 years. METHODS: Blood samples were obtained at predose baseline and at defined intervals up to and including 28 hours after a 5-mg levocetirizine dose. Concurrently, epicutaneous tests with histamine phosphate, 1 mg/mL, were performed. Wheals and flares were traced at 10 minutes, and the areas were measured with a computerized digitizing system. RESULTS: In children aged 8.6 +/- 0.4 years (+/- SEM), the peak levocetirizine concentration was 450 +/- 37 ng/mL, and the time at which peak concentrations occurred was 1.2 +/- 0.2 hours. The terminal elimination half-life was 5.7 +/- 0.2 hours, the oral clearance was 0.82 +/- 0.05 mL/min/kg, and the volume of distribution was 0.4 +/- 0.02 L/kg. Compared with predose areas, the wheals and flares produced by histamine phosphate were significantly decreased from 1 to 28 hours, inclusive (P < .05). Mean maximum inhibition of wheals and flares occurred from 2 to 10 hours (97% +/- 1%) and from 2 to 24 hours (93% +/- 1%), respectively. CONCLUSIONS: Levocetirizine had an onset of action within 1 hour and provided significant peripheral antihistaminic activity for 28 hours after a single dose. Once-daily dosing may be optimal in children aged 6 to 11 years, as it is in adults.