The CAREGENE study: ACE gene I/D polymorphism and effect of physical training on aerobic power in coronary artery disease.
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Alleles↗
Biomedical subjects
R Vlietinck
Publications and source records attributed to R Vlietinck.
Quantitative trait loci for human muscle strength: linkage analysis of myostatin pathway genes.
This study reports the results of a multipoint linkage study that aims to unravel the genetic basis of muscle strength and muscle mass in humans. Myostatin (GDF8) is known to be a strong inhibitor of muscle growth in animals. However, studies examining human myostatin polymorphisms are rare and are limited to the GDF8 gene itself. Here, the contribution to isometric and concentric knee strength of nine key proteins involved in the myostatin pathway is studied in a nonparametric multipoint linkage analysis by means of a variance components and regression method. A sample of 367 healthy young male siblings was phenotyped on an isokinetic dynamometer and genotyped for markers of the myostatin pathway genes. Three of the loci were found significantly linked with a quantitative trait locus (QTL) for knee muscle strength. First, D13S1303 showed replication of an explorative single-point linkage study with a maximum LOD score of 2.7 (P = 0.0002). Second, maximum LOD scores of 3.4 (P = 0.00004) and 3.3 (P = 0.00005) were observed for markers D12S1042 and D12S85, respectively, at 12q12-14. Finally, marker D12S78 showed an LOD score of 2.7 at 12q22-23. We conclude that several genes involved in the myostatin pathway, but not the myostatin gene itself, are important QTLs for human muscle strength. An additional set of valuable candidate genes that were not part of the myostatin pathway was found in the chromosome 12 and 13 genomic regions.
Adolescent↗
Deconstructing the familiality of the emotive component of psychotic experiences in the general population.
OBJECTIVE: Genetic and environmental influences on variation in distress associated with subclinical psychotic experiences were examined. METHOD: A total of 289 twin pairs filled in the Community Assessment of Psychic Experiences, a self-report instrument assessing subclinical positive and negative psychotic experiences and associated distress (distresspos and distressneg). Using structural equation modelling, univariate and bivariate models were fitted. RESULTS: Univariate model fitting showed genetic and non-shared environmental influences on both distresspos and distressneg. Bivariate model fitting showed that 52% of the correlation between the two phenotypes (r=0.46) was because of shared genes and that non-shared environmental factors accounted for 48% of the correlation. CONCLUSION: Liability to psychosis not only refers to the development of psychosis per se, but also to the liability to develop dysfunctional emotional appraisals. The emotive component of psychosis liability involves genetic transmission of a general, non-symptom-specific distress factor that may be a target for molecular genetic research.
Adolescent↗
Epithelioid granulomas, pattern recognition receptors, and phenotypes of Crohn's disease.
INTRODUCTION: Crohn's disease is a chronic inflammatory disorder of the gut. It is assumed that a defective interaction between the bacterial flora of the gut and the innate immune system plays a key role in the pathogenesis of the disease. This may lead to specific histological lesions. The epithelioid granuloma is particularly interesting in this regard as it is also observed in several bacterial infections of the gut. AIMS AND METHODS: We hypothesised that genetic or environmental factors with a known influence on inflammation or immunity would lead to an increased prevalence of granulomas. Therefore, surgical specimens from 161 patients were evaluated for the presence of granulomas. Patients were genotyped for the three single nucleotide polymorphisms in caspase recruitment domain 15 (CARD15)/NOD2 associated with CD and for Asp299Gly in Toll-like receptor 4 (TLR4). RESULTS: The overall prevalence of granulomas was 68.9%. We did not find a significant correlation between granulomas and TLR4 or CARD15 variants. The frequency of granulomas increased with more distal disease (63% small bowel, 72% right colon, 88% left colon, 90% rectum; p=0.01). Granulomas were more frequent in younger patients (odds ratio 0.95 (95% confidence interval 0.92-0.98) p=0.007). CONCLUSION: In this study of 161 well documented CD patients, we found no significant association between CARD15 and TLR4 variants and granulomas. This finding seems to refute our initial hypothesis. However, it may be that additional factors are needed for granuloma development. Granulomas may develop only when specific bacterial components are present. Therefore, future research on granuloma pathogenesis should be orientated towards detection and identification of bacterial components in these lesions.
Adult↗
Low expression VEGF haplotype increases the risk for tetralogy of Fallot: a family based association study.
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Family Health↗
Association of tumour necrosis factor alpha variants with the CF pulmonary phenotype.
BACKGROUND: The pulmonary phenotype in patients with cystic fibrosis (CF), even in those with the same CF transmembrane conductance regulator (CFTR) genotype, is variable and must therefore be influenced by secondary genetic factors as well as environmental factors. Possible candidate genes that modulate the CF lung phenotype may include proinflammatory cytokines. One such protein is tumour necrosis factor alpha (TNFalpha), a member of the immune system. METHODS: Three polymorphic loci in the promoter (-851c/t, -308g/a, -238g/a) and one polymorphic locus in intron 1 (+691g ins/del) of the TNFalpha gene were typed by a single nucleotide primer extension assay in CF patients and healthy controls. Spirometric data and first age of infection with Pseudomonas aeruginosa were collected retrospectively from patients' medical records. RESULTS: An association was found between the TNFalpha +691g ins/del polymorphic locus and severity of CF lung disease. Patients heterozygous for +691g ins and +691g del were more likely to have better pulmonary function (mean (SD) forced expiratory volume in 1 second (FEV1) 79.7 (12.8)% predicted) than patients homozygous for +691g ins (mean (SD) FEV1 67.5 (23.0)% predicted; p = 0.008, mean difference 12.2%, 95% CI 3.5 to 21.0). Also, patients heterozygous for +691g ins and +691g del were more likely to have an older first age of infection with P aeruginosa (mean (SD) 11.4 (6.0) years) than patients homozygous for +691g ins (mean (SD) 8.3 (4.6) years; p = 0.018, mean difference 3.1 years, 95% CI 0.5 to 5.6). An association was also found with the -851c/t polymorphic locus. In the group of patients with more severe FEV1% predicted, a higher proportion of patients were homozygous for the -851c allele than in the other group of patients (p = 0.04, likelihood ratio chi2, odds ratio = 2.4). CONCLUSION: TNFalpha polymorphisms are associated with the severity of CF lung disease in Czech and Belgian patients with CF.
Adolescent↗
Tumour necrosis factor-alpha receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab.
BACKGROUND: The role of tumour necrosis factor-alpha in the pathogenesis of inflammatory bowel disorders is well-known and is underscored by the effectiveness of antitumour necrosis factor-alpha treatment. Tumour necrosis factor-alpha exerts its effect by binding TNFR1 and TNFR2, which genes map to inflammatory bowel disorders susceptibility loci. AIMS AND METHODS: Since TNFR1 and TNFR2 are good candidate genes for inflammatory bowel disorders, we studied the functional TNFR2T587G and the TNFR1A36G mutation in 344 Crohn's disease and 152 ulcerative colitis patients and investigated the relation with disease phenotypes. An association with response to infliximab was evaluated in 166 Crohn's disease patients. RESULTS: The TNFR2 587G allele was more frequent in ulcerative colitis compared with controls (P = 0.03). Both single nucleotide polymorphisms were negatively associated with smoking at diagnosis in Crohn's disease (TNFR1A36G odds ratio: 0.614, 95% confidence interval: 0.452, 0.99 and TNFR2T587G odds ratio: 0.572, 95% confidence interval: 0.820, 0.875). There was a positive association between pancolitis and the TNFR1A36G polymorphism in ulcerative colitis (odds ratio: 5.341, 95% confidence interval: 1.484, 19.39). The biological response to infliximab was lower in patients carrying TNFR1 36G (odds ratio: 0.47, 95% confidence interval: 0.234, 0.946). CONCLUSION: The TNFR2 587G allele was more frequent in ulcerative colitis. Both single nucleotide polymorphisms were negatively associated with smoking in Crohn's disease. A relation between TNFR1A36G and pancolitis was found in ulcerative colitis. There was no clear effect of the polymorphisms on infliximab response although, the TNFR1 minor was associated with a lower response to infliximab.
Adolescent↗
Genome wide scan in a Flemish inflammatory bowel disease population: support for the IBD4 locus, population heterogeneity, and epistasis.
BACKGROUND AND AIMS: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As no linkage was previously found on IBD regions 3, 7, 12, and 16 in Flemish IBD families, a genome wide scan was performed to detect other susceptibility regions in this population. METHODS: A cohort of 149 IBD affected relative pairs, all recruited from the Northern Flemish part of Belgium, were genotyped using microsatellite markers at 12 cM intervals, and analysed by Genehunter non-parametric linkage software. All families were further genotyped for the three main Crohn's disease associated variants in the NOD2/CARD15 gene. RESULTS: Nominal evidence for linkage was observed on chromosomes 1 (D1S197: multipoint non-parametric linkage (NPL) score 2.57, p = 0.004; and at D1S305-D1S252: NPL 2.97, p = 0.001), 4q (D4S406: NPL 1.95, p = 0.03), 6q16 (D6S314: NPL 2.44, p = 0.007), 10p12 (D10S197: NPL 2.05, p = 0.02), 11q22 (D11S35-D11S927: NPL 1.95, p = 0.02) 14q11-12 (D14S80: NPL 2.41, p = 0.008), 20p12 (D20S192: NPL 2.7, p = 0.003), and Xq (DXS990: NPL 1.70, p = 0.04). A total of 51.4% of patients carried at least one NOD2/CARD15 variant. Furthermore, epistasis was observed between susceptibility regions 6q/10p and 20p/10p. CONCLUSION: Genome scanning in a Flemish IBD population found nominal evidence for linkage on 1p, 4q, 10p12, and 14q11, overlapping with other genome scan results, with linkage on 14q11-12 supporting the IBD4 locus. The results further show that epistasis is contributing to the complex model of IBD and indicate that population heterogeneity is not to be underestimated. Finally, NOD2/CARD15 is clearly implicated in the Flemish IBD population.
Chromosomes, Human, Pair 14↗
Polymorphisms in the mannose binding lectin gene affect the cystic fibrosis pulmonary phenotype.
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Adolescent↗
Influence of weight-bearing exercises on bone acquisition in prepubertal monozygotic female twins: a randomized controlled prospective study.
The aim of this study was to determine whether high-impact exercises have an osteogenic effect in 21 prepubertal female monozygotic twins aged 8.7 (SD 0.7) years. Bone mineral density (aBMD), bone mineral content (BMC), bone area, and body composition were derived from DXA. Skeletal maturity was assessed by the Tanner-Whitehouse technique. Anthropometric dimensions (28 dimensions) were measured and also used to derive adiposity and muscularity indices, and information about physical activity was obtained by questionnaire. These measurements were taken before and after the exercise period. The exercise program consisted of high-impact exercises. During 9 months, one girl of each twin pair performed the exercises 3 times a week under supervision of a teacher while their sisters served as control group. At baseline there were no differences between the groups. After 9 months, exercisers (Ex) and controls (Con) had similar increases in height and weight. Significant lower adiposity was observed in the exercise group vs the control group. None of the bone indices differed significantly between the two groups. When the analyses were done for a subgroup of twin pairs (n = 12) who did not participate in high-impact sports during their leisure time, significant differences were obtained for aBMD and BMC of the proximal femur in favor of the exercise group. These results indicate that for prepubertal girls who are not involved in sport activities or who are only involved in low-impact sport activities this exercise program has an osteogenic effect on the proximal femur, but for girls who are already involved in high-impact sports this protocol does not have any additional effect on the bone status.
Absorptiometry, Photon↗
Markers for cardiovascular disease in monozygotic twins discordant for the use of third-generation oral contraceptives.
Oral contraceptives (OC) modulate the risk for developing cardiovascular (CV) diseases. The aim of this study was to determine whether the use of third-generation OC has an impact on markers of CV disease in genetically identical women. We performed an intrapair comparison in 27 monozygotic twin pairs, one of whom was taking third-generation OC, whereas the other was not using OC. Biometric parameters were ascertained and conventional and 24-h ambulatory blood pressure (BP) was recorded. A fasting blood sample was taken for the measurement of glucose, insulin, proinsulin, lipids, and insulin-like growth factor binding protein-1 (IGFBP-1). Insulin resistance and beta-cell function were calculated by homeostasis model assessment (HOMA). A 24-h urine sample for cortisol was obtained. Third-generation OC use increased 24-h ambulatory systolic and diastolic BP by 5.2 and 3.9 mmHg, respectively (both P=0.0003). There was no effect on glucose, insulin and proinsulin levels, and on HOMA parameters, but the IGFBP-1 levels were markedly raised (P=0.0009). The lipid profile showed a 34% increase in triglyceride levels (P < 0.0001), but also a 7% increase in HDL-cholesterol levels (P=0.037). Use of third-generation OC impacts on CV disease markers in young-adult genetically identical women. Some changes are beneficial (increased HDL-cholesterol), whereas others may be deleterious (increased BP and triglyceride levels) or have unknown effects at this time (increased IGFBP-1 levels).
Adult↗
Persistent organochlorine pollutants in human serum of 50-65 years old women in the Flanders Environmental and Health Study (FLEHS). Part 1: Concentrations and regional differences.
In 1999, a campaign of the Flemish Ministry of Health, Belgium was set up to assess pollutant concentrations and related health effect biomarkers in humans living in two regions of Flanders. The study was called the 'Flemish Environment and Health Study' (FLEHS). One of the goals was to measure present concentrations of persistent organochlorine pollutants in a Flemish population and to compare values obtained from pooled and individual serum samples. Concentrations of selected organochlorine pesticides, polychlorinated biphenyls (PCB) and polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) were measured by gas chromatography-mass spectrometry. TEQ values were also assessed by Chemical-Activated LUciferase gene eXpression (CALUX) bioassay. The study population consisted of 200 women between 50 and 65 years living in two areas of Flanders, Belgium. Because of the large volumes serum needed for all measurements, the concentrations of organochlorines were measured in 47 pooled serum samples originating from these women. The concentrations of the indicator PCBs (359.8 ng/g fat) and organochlorine pesticides (hexachlorobenzene, p,p'-dichlorodiphenyldichloroethylene, p,p'-dichlorodiphenyl-trichloroethane, lindane and pentachlorophenol), were comparable to those found in other European countries. The concentrations of PCDD/PCDFs showed another picture. With a median value of 48 pg WHO-TEQ/g fat, the women had 2-fold higher levels than a comparable age group from Germany examined in 1996. The mean total WHO-TEQ including PCDD/F, non-ortho and mono-ortho PCBs was 72.7 pg WHO-TEQ/g fat, whereas the CALUX-TEQ mean value was only 35.0 pg TEQ/g fat. In order to assess the pooling procedure, indicator PCBs and CALUX-TEQs were measured in all 200 individuals that were integrated in the pools. The measured values were comparable to the pool results: 390.0 ng/g fat and 41.6 pg TEQ/g fat respectively. It was concluded that pooling of serum samples offers the possibility to measure exposure in the whole study population on a more cost-effective way. However, because of statistical power loss and no possibility of confounder adjustment, pooling is not the most effective way to study regional differences.
Aged↗
Prenatal life and post-natal psychopathology: evidence for negative gene-birth weight interaction.
BACKGROUND: Many studies suggest that pregnancy and birth complications (PBCs) are environmental risk factors for child psychopathology. However, it is not known whether the effects of PBCs occur independently of genetic predisposition. The current study examined the possibility of gene-environment interaction in a twin design. METHOD: The East Flanders Prospective Twin Survey prospectively records the births of all twin pairs born in East Flanders, Belgium. The current study included 760 twin pairs aged 6-17 years. Multilevel regression analysis was used to assess the effects of several PBCs collected around the time of birth. Using structural equation modelling, ACE models assuming additive genetic (A), shared environmental (C) and unique environmental (E) influences, were compared in order to examine whether the contribution of genetic factors to parent-rated child problem behaviour varied as a function of exposure to dichotomously and continuously defined PBCs. RESULTS: A main independent effect of lower birth weight, corrected for gestational age (small for gestational age--SGA), on child problem behaviour was found. In addition, there was an interaction between genetic influence and SGA, in that being smaller for gestational age resulted in less influence of additive genetic factors on individual differences in problem behaviour. CONCLUSIONS: Results are suggestive of negative gene-birth weight interaction. Children who are SGA are less sensitive to the genetic effects, and those with high genetic vulnerability are less sensitive to the effects of being SGA in bringing about post-natal mental health effects.
Adolescent↗
Heritability of plasma renin activity and plasma concentration of angiotensinogen and angiotensin-converting enzyme.
The purpose of the present investigation was to describe the relative impact of genes and environment on the variance of the plasma constituents of the renin angiotensin system. We ascertained 56 male and 80 female adult same-sex twin pairs from the Flemish population. Plasma renin activity (PRA), the concentration of angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) were measured, and path analysis was applied, after transformation toward normality. For PRA and AGT significant heritability was only detected in the male subgroup, with heritability estimates of 66% and 90%, respectively. Angiotensin-converting enzyme concentration was determined by additive genes for 43% of its variance, by shared environmental influences for 42%, and by specific environmental influences for 15%. The high heritability found for AGT is compatible with the results of earlier studies linking the M235T polymorphism of the angiotensinogen gene to plasma AGT levels. For PRA, we are the first to show significant heritability. Our results regarding ACE confirm the findings in other populations.
Aged↗
Child psychopathology and lower cognitive ability: a general population twin study of the causes of association.
Previous work has demonstrated associations between lower cognitive ability and childhood and adult non-psychotic psychopathology. As both cognitive ability (CA) and child psychopathology (CP) are influenced by genetic factors, one explanation for the association is that they are the pleiotropic manifestations of the same underlying genetic factors. The present paper examines three possible causes of the association: additive genetic factors, common environmental factors and individual-specific environmental factors. Three hundred and seventy-six twin pairs from the East Flanders Prospective Twin Survey were examined with the Child Behaviour Checklist and the Wechsler Intelligence Scale for Children-Revised. The cross-twin within-variable, within-twin cross-variable and cross-twin cross-variable correlations were calculated. Using structural equation modelling, bivariate models were fitted. The best fitting model was chosen, based on likelihood and parsimony. The observed phenotypic correlation between CP and CA was -0.19 (95% CI: -0.09, -0.27), with genetic factors accounting for about 84% of the observed correlation. Bivariate model fitting quantified the genetic correlation between CP and CA at -0.27 (95% CI: -0.12, -0.42) and the individual-specific environmental correlation at -0.17 (95% CI: -0.03, -0.31). In children, three different genetic factors may exist: one that solely affects the liability to CP, one that has only an effect on CA and one that influences both CP and CA. While individual-specific environmental factors can influence the liability to both traits, our results suggest that most of the environmental factors that increase the risk of CP do not influence CA and vice versa.
Adolescent↗
Body composition estimations by BIA versus anthropometric equations in body builders and other power athletes.
BACKGROUND: Two main questions are stated: 1) are BIA and anthropometric equations accurate in estimating body composition in male power athletes and more specifically in body builders and 2) is there a difference in body composition when body builders are compared to weight and power lifters? METHODS EXPERIMENTAL DESIGN: this is a descriptive, comparative study on a selected sample of power athletes. PARTICIPANTS: 49 Belgian elite and sub-top male power athletes (34 body builders and 15 weight and power lifters) were included in this sample. More than 70% was in preparation of competition at time of data collection. MEASURES: an extended set of anthropometric measures was taken. Body composition was estimated by BIA (Bioelectrical Impedance Analysis) and by regression equations of skinfolds. Somatotype and muscle+bone areas were calculated. Factor analysis on all anthropometric measures was carried out to determine the body structure of the athletes. RESULTS: Compared to external visual criteria, the equations of Durnin and Womersley and Lohman (skinfolds) and the Guo-equation (BIA) were the only equations that could accurately estimate the body composition for this specific group of athletes. However, the sum of skinfolds attains the most accurate estimate of subcutaneous fatness. Body builders have significantly (p<0.01) larger arm and thigh circumferences and are more mesomorfic than the other power athletes (5.9 vs 3.8). CONCLUSIONS: This study shows that to estimate body composition in extreme power athletes BIA is not as accurate as compared to anthropometric equations. Moreover, the sum of a larger set of skinfolds is preferred to anthropometric prediction equations. In addition, body builders are more muscular and leaner than other power athletes.
Adipose Tissue↗
A prospective twin study of birth weight discordance and child problem behavior.
BACKGROUND: We investigated whether low birth weight constitutes a causal risk factor for child problem behavior, using a variation of the co-twin control method. METHODS: In a representative sample of 745 twin pairs (monozygotic: 324 pairs), birth weight was recorded at birth and child problem behavior at mean age 10 years was measured with the Child Behaviour Checklist (CBCL). RESULTS: Lower birth weight was a continuous risk factor for later child problem behavior (adjusted regression coefficient over units of 500 g: beta = -.15, p =.046), and greater levels of within-pair CBCL discordance did not result in a reduced effect size. Greater within-pair birth weight discordance was associated with greater within-pair CBCL score discordance (beta =.35, p <.001). This latter effect was similar in monozygotic (beta =.34, p =.005) and dizygotic twins (beta =.37, p =.003). CONCLUSIONS: The fact that (1) the effect size of the association between low birth weight and child problem behavior was not reduced in pairs with greater levels of CBCL discordance, and (2) similar effect sizes were found in monozygotic and dizygotic twins for the within-pair association between birth weight discordance and CBCL score discordance, suggests that the observed relationship between low birth weight and child problem behavior is not due to a shared environmental or genetic variable that influences both characteristics. Lower birth weight is a causal risk factor for child problem behavior, the effects of which may well extend into adulthood.
Adolescent↗
Birth weight and blood pressure in young adults: a prospective twin study.
BACKGROUND: The intrauterine environment may be a critical period for the development of hypertension in later life. In the present study, we applied the twin approach to estimate the contribution of genetic and environmental causes that may underlie the birth weight-adult blood pressure association. METHODS AND RESULTS: Birth weights of 418 twin pairs were obtained prospectively, and resting and 24-hour ambulatory blood pressures were obtained at the age of 18 to 34 years. In women, resting systolic blood pressure decreased 4.27 mm Hg (P<0.001) and diastolic pressure decreased 2.18 mm Hg (P=0.02) per kilogram increase in birth weight. Similar associations were found for ambulatory measurements, although these were somewhat less pronounced. Pair-wise analysis confirmed these findings: twin pairs of whom both members had a low birth weight (<2500 g) had a higher systolic blood pressure compared with twins who both had a high birth weight (>/=2500 g). Systolic blood pressure of the lightest of a low-birth-weight pair was >/=4.7 mm Hg (P=0.02) higher and of the heaviest >/=2.4 mm Hg higher (P=0.2) than similar measurements in high-birth-weight pairs. Intrapair differences in blood pressure between the lightest and the heaviest at birth were only present in low-birth-weight pairs. The results were similar for monozygotic and dizygotic twin pairs. In men, no associations were found between birth weight and adult blood pressure. CONCLUSIONS: These findings suggest that prenatal programming of adult blood pressure occurs at least in female twins. We suggest that particularly maternal influences, experienced by both twin members, may underlie the association between birth weight and blood pressure. The fetoplacental unit seems to influence blood pressure only when both fetuses had low birth weight.
Adolescent↗