Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Monitoring pilot Houtribdijk
    Penning, Ellis ; Bijlsma, Penning ; Heijer, Kees den; Lange, Marieke de; Vuik, Vincent - \ 2018
    Delft : Deltares - 159
    Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
    Jiang, Xia ; O'Reilly, Paul F. ; Aschard, Hugues ; Hsu, Yi Hsiang ; Richards, J.B. ; Dupuis, Josée ; Ingelsson, Erik ; Karasik, David ; Pilz, Stefan ; Berry, Diane ; Kestenbaum, Bryan ; Zheng, Jusheng ; Luan, Jianan ; Sofianopoulou, Eleni ; Streeten, Elizabeth A. ; Albanes, Demetrius ; Lutsey, Pamela L. ; Yao, Lu ; Tang, Weihong ; Econs, Michael J. ; Wallaschofski, Henri ; Völzke, Henry ; Zhou, Ang ; Power, Chris ; McCarthy, Mark I. ; Michos, Erin D. ; Boerwinkle, Eric ; Weinstein, Stephanie J. ; Freedman, Neal D. ; Huang, Wen Yi ; Schoor, Natasja M. van; Velde, Nathalie van der; Groot, Lisette C.P.G.M. de; Enneman, Anke ; Cupples, L.A. ; Booth, Sarah L. ; Vasan, Ramachandran S. ; Liu, Ching Ti ; Zhou, Yanhua ; Ripatti, Samuli ; Ohlsson, Claes ; Vandenput, Liesbeth ; Lorentzon, Mattias ; Eriksson, Johan G. ; Shea, M.K. ; Houston, Denise K. ; Kritchevsky, Stephen B. ; Liu, Yongmei ; Lohman, Kurt K. ; Ferrucci, Luigi ; Peacock, Munro ; Gieger, Christian ; Beekman, Marian ; Slagboom, Eline ; Deelen, Joris ; Deelen, Joris ; Heemst, Diana van; Kleber, Marcus E. ; März, Winfried ; Boer, Ian H. De; Wood, Alexis C. ; Rotter, Jerome I. ; Rich, Stephen S. ; Robinson-Cohen, Cassianne ; Heijer, Martin Den; Jarvelin, Marjo Riitta ; Jarvelin, Marjo Riitta ; Cavadino, Alana ; Cavadino, Alana ; Joshi, Peter K. ; Wilson, James F. ; Hayward, Caroline ; Lind, Lars ; Michaëlsson, Karl ; Trompet, Stella ; Zillikens, M.C. ; Uitterlinden, Andre G. ; Rivadeneira, Fernando - \ 2018
    Nature Communications 9 (2018)1. - ISSN 2041-1723
    Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10 -9 at rs8018720 in SEC23A, and P = 1.9×10 -14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
    Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis
    Manousaki, Despoina ; Dudding, Tom ; Haworth, Simon ; Hsu, Yi Hsiang ; Liu, Ching Ti ; Medina-Gómez, Carolina ; Voortman, Trudy ; Velde, Nathalie Van Der; Melhus, Håkan ; Vandenput, Liesbeth ; Noordam, Raymond ; Forgetta, Vincenzo ; Greenwood, Celia M.T. ; Biggs, Mary L. ; Psaty, Bruce M. ; Rotter, Jerome I. ; Zemel, Babette S. ; Mitchell, Jonathan A. ; Taylor, Bruce ; Lorentzon, Mattias ; Karlsson, Magnus ; Jaddoe, Vincent W.V. ; Tiemeier, Henning ; Campos-Obando, Natalia ; Franco, Oscar H. ; Utterlinden, Andre G. ; Broer, Linda ; Schoor, Natasja M. van; Ham, Annelies C. ; Ikram, Arfan M.A. ; Karasik, David ; Mutsert, Renée De; Rosendaal, Frits R. ; Heijer, Martin den; Wang, Thomas J. ; Lind, Lars ; Orwoll, Eric S. ; Mook-Kanamori, Dennis O. ; Michaëlsson, Karl ; Kestenbaum, Bryan ; Ohlsson, Claes ; Mellström, Dan ; Groot, Lisette C.P.G.M. de; Grant, Struan F.A. ; Kiel, Douglas P. ; Zillikens, M.C. ; Rivadeneira, Fernando ; Sawcer, Stephen ; Timpson, Nicholas J. ; Richards, J.B. - \ 2017
    American Journal of Human Genetics 101 (2017)2. - ISSN 0002-9297 - p. 227 - 238.
    GWAS - Low-frequency genetic variants - Multiple sclerosis - Vitamin D
    Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 × 10-88). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 × 10-12). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 × 10-5) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.
    Fatty acid intake and its dietary sources in relation with markers of type 2 diabetes risk : The NEO study
    Wanders, A.J. ; Alssema, M. ; Koning, E.J.P. de; Cessie, S. Le; Vries, J.H. de; Zock, P.L. ; Rosendaal, F.R. ; Heijer, M. den; Mutsert, R. de - \ 2017
    European Journal of Clinical Nutrition 71 (2017)2. - ISSN 0954-3007 - p. 245 - 251.

    Objective: The aim of this study was to examine the relations between intakes of total, saturated, mono-unsaturated, poly-unsaturated and trans fatty acids (SFA, MUFA, PUFA and TFA), and their dietary sources (dairy, meat and plant) with markers of type 2 diabetes risk. Subjects/Methods: This was a cross-sectional analysis of baseline data of 5675 non-diabetic, middle-aged participants of the Netherlands Epidemiology of Obesity (NEO) study. Associations between habitual dietary intake and fasting and postprandial blood glucose and insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), HOMA of β-cell function (HOMA-B) and Disposition Index were assessed through multivariable linear regression models with adjustments for demographic, lifestyle and dietary factors. Results: Mean (s.d.) intakes in percent of energy (En%) were 34.4 (5.8) for total fatty acids, 12.4 (2.9) for SFA, 12.2 (2.4) for MUFA, 6.9 (1.9) for PUFA and 0.6 (0.2) for TFA. As compared with carbohydrates, only SFA was weakly inversely associated with fasting insulin, HOMA-IR and HOMA-B. When stratified by dietary source, all fatty acids from meat were positively associated with fasting insulin-total fatty acidsmeat (per 5 En%: 10.0%; 95% confidence interval: 4.0, 16.3), SFAmeat (per 1 En%: 3.7%; 0.4, 7.2), MUFAmeat (per 1 En%: 5.0%; 2.0, 8.1), PUFAmeat (per 1 En%: 17.3%; 6.0, 29.7) and TFAmeat (per 0.1 En%: 10.5%; 3.2, 18.3). Similarly, all fatty acids from meat were positively associated with HOMA-IR and HOMA-B and inversely with Disposition Index. Conclusions: Our study suggests that the relations between fatty acid intakes and markers of type 2 diabetes risk may depend on the dietary sources of the fatty acids. More epidemiological studies on diet and cardiometabolic disease are needed, addressing possible interactions between nutrients and their dietary sources.

    Netinnovatie Kottervisserij
    Marlen, B. van; Molenaar, P. ; Bol, R.A. ; Dammers, M. ; Groeneveld, K. ; Machiels, M.A.M. ; Heijer, W.M. den - \ 2016
    IMARES (Rapport / IMARES C110/15) - 130
    visserij - boomkorvisserij - bijvangst - vangstsamenstelling - fisheries - beam trawling - bycatch - catch composition
    Als reactie op de aanlandplicht heeft de kottersector via de Coöperatieve Visserij Organisatie (CVO) het initiatief opgepakt om de selectiviteit van de vistuigen te verhogen om zo weinig mogelijk discards te vangen en aan te landen. Na een ontwerpfase met modelonderzoek in de flume tank van SINTEF te Hirtshals, Denemarken, en met ervaringen uit eerdere projecten werden op verscheidene schepen netinnovaties uitgeprobeerd. Er werd onderzoek gedaan op een schip met boomkor, verschillende schepen vissend met pulsvistuigen en op twinriggers. Hierbij werd aanvankelijk gewerkt op ‘trial-and error’ basis met in sommige gevallen zelfmonitoring. Vervolgens werden enkele uitgebreide vangst- en bijvangstvergelijkingen gedaan met medewerkers van IMARES aan boord.
    Long-term vitamin D deficiency in older adult C57BL/6 mice does not affect bone structure, remodeling and mineralization
    Meijden, K. ; Buskermolen, J. ; Essen, H. van; Schuurman, Teun ; Steegenga, W.T. ; Brouwer, E.M. ; Langenbach, G.E.J. ; Ruijven, L.J. van; Heijer, M. den; Lips, P. ; Bravenboer, N. - \ 2016
    Journal of Steroid Biochemistry and Molecular Biology 164 (2016). - ISSN 0960-0760 - p. 344 - 352.
    Animal models show that vitamin D deficiency may have severe consequences for skeletal health. However, most studies have been performed in young rodents for a relatively short period, while in older adult rodents the effects of long-term vitamin D deficiency on skeletal health have not been extensively studied. Therefore, the first aim of this study was to determine the effects of long-term vitamin D deficiency on bone structure, remodeling and mineralization in bones from older adult mice. The second aim was to determine the effects of long-term vitamin D deficiency on mRNA levels of genes involved in vitamin D metabolism in bones from older adult mice. Ten months old male C57BL/6 mice were fed a diet containing 0.5% calcium, 0.2% phosphate and 0 (n = 8) or 1 (n = 9) IU vitamin D3/gram for 14 months. At an age of 24 months, mice were sacrificed for histomorphometric and micro-computed tomography (micro-CT) analysis of humeri as well as analysis of CYP27B1, CYP24 and VDR mRNA levels in tibiae and kidneys using RT-qPCR. Plasma samples, obtained at 17 and 24 months of age, were used for measurements of 25-hydroxyvitamin D (25(OH)D) (all samples), phosphate and parathyroid hormone (PTH) (terminal samples) concentrations. At the age of 17 and 24 months, mean plasma 25(OH)D concentrations were below the detection limit (<4 nmol/L) in mice receiving vitamin D deficient diets. Plasma phosphate and PTH concentrations did not differ between both groups. Micro-CT and histomorphometric analysis of bone mineral density, structure and remodeling did not reveal differences between control and vitamin D deficient mice. Long-term vitamin D deficiency did also not affect CYP27B1 mRNA levels in tibiae, while CYP24 mRNA levels in tibiae were below the detection threshold in both groups. VDR mRNA levels in tibiae from vitamin D deficient mice were 0.7 fold lower than those in control mice. In conclusion, long-term vitamin D deficiency in older adult C57BL/6 mice, accompanied by normal plasma PTH and phosphate concentrations, does not affect bone structure, remodeling and mineralization. In bone, expression levels of CYP27B1 are also not affected by long-term vitamin D deficiency in older adult C57BL/6 mice. Our results suggest that mice at old age have a low or absent response to vitamin D deficiency probably due to factors such as a decreased bone formation rate or a reduced response of bone cells to 25(OH)D and 1,25(OH)2D. Older adult mice may therefore be less useful for the study of the effects of vitamin D deficiency on bone health in older people.
    Bijdragen nationale projecten aan de belevings- en natuurwaarde van het Nederlandse landschap : Tussenrapportage WOT-04-010-036.59
    Pleijte, M. ; During, R. ; Heijer, Arie-Benjamin den - \ 2015
    Wageningen : WOT Natuur & Milieu (WOt-interne notitie 132) - 54 p.
    Book review of Henk den Heijer, Geschiedenis van de WIC. Opkomst, bloei en ondergang
    Frankema, E.H.P. - \ 2013
    Tijdschrift voor Sociale en Economische Geschiedenis = The Low Countries Journal of Social and Economic History 10 (2013). - ISSN 1572-1701 - p. 129 - 130.
    Total antioxidant capacity of the diet and major neurologic outcomes in older adults
    Devore, E.E. ; Feskens, E.J.M. ; Ikram, M.A. ; Heijer, T. den; Vernooij, M. ; Lijn, F. van der; Hofman, A. ; Niessen, W.J. ; Breteler, M.M.B. - \ 2013
    Neurology 80 (2013)10. - ISSN 0028-3878 - p. 904 - 910.
    food-frequency questionnaire - alzheimers-disease - cardiovascular-disease - hippocampal atrophy - ischemic-stroke - rotterdam - risk - dementia - metaanalysis - association
    Objective: To evaluate total antioxidant capacity of the diet, measured by the ferric-reducing antioxidant power (FRAP) assay, in relation to risks of dementia and stroke, as well as key structural brain volumes, in the elderly. Methods: We prospectively studied 5,395 participants in the Rotterdam Study, aged 55 years and older, who were dementia free and provided dietary information at study baseline; 5,285 individuals were also stroke free at baseline, and 462 were dementia and stroke free at the time of an MRI brain scan 5 years after baseline. Dietary data were ascertained using a semiquantitative food-frequency questionnaire, and combined with food-specific FRAP measurements from published tables; this information was aggregated across the diet to obtain “dietary FRAP scores.” Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks of dementia and stroke, and multivariable-adjusted linear regression was used to estimate mean differences in structural brain volumes, across tertiles of dietary FRAP scores. Results: During a median 13.8 years of follow-up, we identified approximately 600 cases each of dementia and stroke. In multivariable-adjusted models, we observed no associations between dietary FRAP scores and risk of dementia (p trend = 0.3; relative risk = 1.12, 95% confidence interval = 0.91–1.38, comparing the highest vs lowest FRAP tertiles) or risk of stroke (p trend = 0.3; relative risk = 0.91, 95% confidence interval = 0.75–1.11, comparing extreme FRAP tertiles); results were similar across subtypes of these outcomes. Dietary FRAP scores were unrelated to brain tissue volumes as well. Conclusions: Total antioxidant capacity of the diet, measured by dietary FRAP scores, does not seem to predict risks of major neurologic diseases
    Blood lipid levels and prostate cancer risk; a cohort study
    Kok, D.E.G. ; Roermund, J.G.H. van; Aben, K.K.H. ; Heijer, M. den; Swinkels, D.W. ; Kampman, E. ; Kiemeney, L.A.L.M. - \ 2011
    Prostate Cancer and Prostatic Diseases 14 (2011)4. - ISSN 1365-7852 - p. 340 - 345.
    density-lipoprotein cholesterol - serum-cholesterol - prevention trial - national-health - lowering drugs - statin use - plasma - cells - rafts - men
    It has been hypothesized that blood lipid levels might be associated with prostate cancer risk. The aim of the present study was to evaluate the association between serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and prostate cancer risk in a cohort study among 2842 Dutch men. By the end of follow-up, 64 incident cases of prostate cancer were identified. Serum total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were evaluated as potential risk factors for prostate cancer using multivariable Cox proportional hazards regression models. These analyses were restricted to men who never used cholesterol-lowering drugs (2118 men, 43 cases). Higher total and higher LDL cholesterol were significantly associated with an increased risk of prostate cancer (hazards ratios (HR) and 95% confidence interval (CI) per mmol l(-1) were 1.39 (95% CI 1.03-1.88) and 1.42 (95% CI 1.00-2.02), respectively). Similar results were observed for aggressive prostate cancer, whereas for non-aggressive prostate cancer a significant association with HDL cholesterol was found (HR 4.28, 95% CI 1.17-15.67). The results of this study suggest that blood lipid levels may influence risk of prostate cancer. However, the exact roles of different cholesterol fractions on prostate cancer aggressiveness should be further evaluated. Prostate Cancer and Prostatic Diseases (2011) 14, 340-345; doi:10.1038/pcan.2011.30; published online 5 July 2011
    Het voedsellandschap van de Zuidvleugel
    Schans, J.W. van der; Heijer, I. den; Krieger, J. de - \ 2010
    Provincie Zuid-Holland, WUR LEI, JK Ontwerp & Onderzoek (& Eetbaar Rotterdam) - 38
    stadslandbouw - stedelijke gebieden - regionale voedselketens - voedselproductie - relaties tussen stad en platteland - rijnmondgebied - urban agriculture - urban areas - regional food chains - food production - rural urban relations - rijnmondgebied
    Dit boekje is een inventarisatie van bedrijven en initiatieven in en rond het stedelijke gebied die zich richten op voedselproductie voor voornamelijk de lokale markt.
    Verantwoord diergebruik in veldonderzoek
    Heijer, M.E. den; Berghuis, M. ; Wijk, B.B.H. van - \ 2010
    dierenwelzijn - experimenteel veldonderzoek - dierproeven - laboratoriumdieren - animal welfare - field experimentation - animal experiments - laboratory animals
    Tegenwoordig wordt er bij ecologisch en biologisch veldonderzoek steeds meer gebruik gemaakt van (non)invasieve onderzoeksmethoden variërend van bijvoorbeeld het vangen, merken, verdoven, inbrengen van een zender tot het afnemen van bloed bij dieren. De huidige artikel 12 opleidingen (ex Wod) zijn gericht op handelingen aan dieren in biomedische experimenten. Echter de handelingen in veldbiologische experimenten zijn anders van aard en dat vereist specifieke kennis van de werknemer om het dierenwelzijn te waarborgen.
    Artikel 12 Wildlife
    Heijer, M. den - \ 2010
    dierenwelzijn - dierproeven - wilde dieren - laboratoriumdieren - biotechnologie - experimenteel veldonderzoek - leerplan - professionaliteit - vaardigheden - agrarisch onderwijs - animal welfare - animal experiments - wild animals - laboratory animals - biotechnology - field experimentation - curriculum - professionalism - skills - agricultural education
    Tegenwoordig wordt er bij ecologisch en biologisch veldonderzoek al meer gebruik gemaakt van (non)invasieve onderzoeksmethoden variërend van bijvoorbeeld het vangen, merken, verdoven, inbrengen van een zender tot het afnemen van bloed bij dieren. De huidige artikel 12 opleidingen zijn gericht op handelingen aan dieren in biomedische experimenten. Echter de handelingen in veldbiologische experimenten zijn anders van aard en dat vereist specifieke kennis van de werknemer om het dierenwelzijn te waarborgen. Het hoofddoel van het project Artikel 12 Wildlife is het ontwikkelen van een curriculum ‘Artikel 12 Wildlife’ dat past binnen het huidige Bama stelsel. Dit om te voorzien in de vraag naar kundig personeel die dergelijke handelingen aan in het wild levende (proef)dieren kunnen en mogen verrichten.
    Tussenrapportage Artikel 12 Wildlife
    Heijer, M.E. den - \ 2009
    dierenwelzijn - dierproeven - wilde dieren - experimenteel veldonderzoek - leerplan - professionaliteit - vaardigheden - agrarisch onderwijs - leerplanontwikkeling - laboratoriumdieren - animal welfare - animal experiments - wild animals - field experimentation - curriculum - professionalism - skills - agricultural education - curriculum development - laboratory animals
    In maart 2009 is het KIGO project Artikel 12 Wildlife van start gegaan. Dit project is onderdeel van het GKC programma ‘Welzijn van dieren’. Aanleiding voor dit project is dat in toenemende mate bij ecologisch en biologisch veldonderzoek gebruik gemaakt van wordt van (non)invasieve onderzoeksmethoden variërend van bijvoorbeeld het vangen, merken, verdoven, inbrengen van een zender tot het afnemen van bloed. Hierbij is mogelijk sprake van enig ongerief voor de dieren. Formeel vallen een aantal van deze handelingen onder de Wet op de Dierproeven (Wod) en moet degene die deze handelingen verricht bevoegd zijn voor het uitvoeren daarvan (artikel 9 of 12 status ex Wod). Op dit moment zijn er in de Wod nog geen aparte bepalingen voor werkenden in de veldbiologische sector opgenomen. Er is echter sprake van toenemende maatschappelijke belangstelling voor een maatschappelijk verantwoorde ethische behandeling van dieren.
    Common 894G>T single nucleotide polymorphism in the gene coding for endothelial nitric oxide synthase (eNOS) and risk of congenital heart defects
    Beynum, I.M. van; Mooij, C. ; Kapusta, L. ; Heil, S.G. ; Heijer, M. den - \ 2008
    Clinical Chemistry and Laboratory Medicine 46 (2008)10. - ISSN 1434-6621 - p. 1369 - 1375.
    periconceptional multivitamin supplementation - cardiovascular-disease - homocysteine metabolism - scientific statement - current knowledge - association - genotype - disequilibrium - mechanisms - expression
    BACKGROUND: Endothelial nitric oxide synthase (eNOS) produces nitric oxide, which plays a role in vasodilatation and in the regulation of cell growth and apoptosis. eNOS-deficient mice have impaired cardiac development resulting in congenital heart defects (CHDs). In humans, a single nucleotide polymorphism in the gene coding for eNOS (894G>T) is associated with birth defects. METHODS: We investigated the eNOS 894G>T polymorphism in relation to CHDs using a case-control study and a case-parent study. Possible interaction with maternal cigarette smoking during pregnancy and periconceptional folic acid supplementation was also investigated in a case-only approach. RESULTS: The eNOS 894G>T polymorphism was genotyped in 170 CHD-affected children, in 161 of their mothers, 215 control children and 240 control women. For the case-parent study, 135 complete triads were available. The sum of eNOS 894 GT and TT vs. GG genotypes in children was associated with increased CHD risk [odds ratio, OR 1.5 (95% CI 1.03-2.31)]. There was no preferential transmission of the 894T allele [OR 1.2 (95% CI 0.81-1.69)]. Overall, the maternal eNOS 894 GT or TT vs. GG genotypes were not associated with increased CHD risk. The maternal 894TT genotype in combination with maternal smoking was associated with an increased risk, particularly for a subgroup of other than conotruncal heart defects [OR 3.3 (95% CI 1.00-11.1)]. No interaction with periconceptional folic acid supplementation was observed. CONCLUSIONS: Our data indicate that the eNOS 894G>T polymorphism is associated with increased CHD risk. The study also provides evidence of a possible gene-environment interaction effect on CHD risk between the maternal eNOS 894G>T variant and maternal cigarette smoking during pregnancy. This observation should be interpreted with caution because of the relatively small subgroups. Further study in a larger group of CHD subjects is required.
    Role for mitochondrial uncoupling protein-2 (UCP2) in hyperhomocysteinemia and venous thrombosis risk?
    Heil, S.G. ; Vermeulen, S.H. ; Rijt-Pisa, B.J. ; Heijer, M. den; Blom, H.J. - \ 2008
    Clinical Chemistry and Laboratory Medicine 46 (2008)5. - ISSN 1434-6621 - p. 655 - 659.
    homocysteine - translocation - metaanalysis - activation - obesity - disease - trial - cells - mthfr
    Background: Hyperhomocysteinemia has been associated with an increased risk of venous thrombosis, which might be mediated through an oxidative stress dependent mechanism. The function of uncoupling protein-2 (UCP2) is still under debate, but it has been suggested to play a role in reduction of mitochondrial reactive oxygen species. In the present study, we investigated whether the 45 bp deletion/insertion (del/ins) polymorphism in the UCP2 gene is associated with elevated homocysteine levels and whether it might be associated with an increased risk of recurrent venous thrombosis (RVT). Methods: The 45 bp del/ins polymorphism in the UCP2 gene was genotyped by PCR analysis in 161 RVT cases and 386 controls of Caucasian origin in which fasting- and post-load homocysteine levels were previously determined. Statistical analysis was performed to assess whether the UCP2 45 bp del/ins polymorphism was associated with plasma total homocysteine levels and venous thrombosis risk. Results: Post-load homocysteine levels were positively associated with UCP2 45 bp ins/ins genotype (p=0.02). None of the UCP2 45 bp ins/del genotypes were associated with fasting plasma homocysteine levels. The frequency of the UCP2 45 bp ins/ins genotype was 12.4% in RVT cases compared to 8.3% in controls, which resulted in an odds ratio of 1.8 (95% CI 1.0¿3.4). Conclusions: The results of our study show that the common 45 bp del/ins polymorphism in the UCP2 gene is associated with hyperhomocysteinemia, which might increase the risk of venous thrombosis. However, the mechanism is not fully understood and additional studies should be performed to confirm our findings.
    Inhibition of methylation and changes in gene expression in relation to neural tube defects
    Linden, I.J. van der; Heil, S.G. ; Egmont-Petersen, M. van; Straaten, H.W. ; Heijer, M. den - \ 2008
    Birth defects research. Part A, Clinical and molecular teratology 82 (2008)10. - ISSN 1542-0752 - p. 676 - 683.
    factor-i - methylenetetrahydrofolate reductase - serine/threonine kinase - caenorhabditis-elegans - mammalian development - common mutation - risk-factor - dna - serine - folate
    BACKGROUND: An impaired DNA methylation has been suggested to underlie the complex etiology of neural tube defects (NTDs). Previously, we have demonstrated that inhibition of methylation by periodate oxidized adenosine (Adox) results in a widening of the anterior neuropore (ANP) in our in vitro chick embryo model. Since DNA methylation is the chief regulator of gene expression, we hypothesize that inhibition of methylation by Adox in our in vitro chick embryo model will affect the expression of genes that may be involved in neurulation. In the present study, we therefore examined differential gene expression between Adox-treated and control chick embryos, using the Affymetrix Genechip Chicken Genome Array. METHODS: Chick embryos of 4/5 somites were cultured in vitro with saline (control) or Adox and cranial parts were excised. Gene expression profiling was determined using the Affymetrix Genechip Chicken Genome Array on RNA isolated from two pools of Adox-treated cranial parts (n = 12) and two pools of saline-treated cranial parts (n = 12). Microarray data were validated by QPCR analysis. RESULTS: In the Adox-treated chick embryos, 45 probesets were up-regulated (fold 2.0, p <0.05) and 32 probesets were down-regulated (fold 0.5, p <0.05). Of the 15 genes selected for QPCR analysis, the up-regulation of phosphoserine phosphatase (PSPH), unc-51-like kinase 1 (ULK1), and chemokine (C-X-C motif) ligand 12/stromal cell-derived factor 1 (CXCL12/SDF-1) was confirmed. CONCLUSIONS: Inhibition of methylation by Adox affects gene expression in our in vitro chick embryo model. Further research will focus on the gene-specific methylation patterns of PSPH, ULK1, and CXCL12/SDF-1 and the role of the products of these genes in neurulation.
    Equine aquatraining, the effect of water level on impact forces
    Haazelager, M. ; Muller, M. ; Janssen, E. ; Heijer, G. den; Heeck, K. ; Leeuwen, J.L. van - \ 2008
    In: Comparative Biochemistry and Physiology, Part A. Abstracts of the Annual Main Meeting of the Society for Experimental Biology, 6th - 10th July 2008, Marseille, France. - Elsevier - p. S82 - S82.
    The arms race between fishers
    Rijnsdorp, A.D. ; Poos, J.J. ; Quirijns, F.J. ; Hille Ris Lambers, R. ; Wilde, J.W. de; Heijer, W.M. den - \ 2008
    Journal of Sea Research 60 (2008)1-2. - ISSN 1385-1101 - p. 126 - 138.
    north-sea plaice - hake merluccius-bilinearis - maturation reaction norms - fishing vessels - mixed fisheries - fleet dynamics - behavioral inferences - population-dynamics - beam trawlers - catch
    An analysis of the changes in the Dutch demersal fishing fleet since the 1950s revealed that competitive interactions among vessels and gear types within the constraints imposed by biological, economic and fisheries management factors are the dominant processes governing the dynamics of fishing fleets. Double beam trawling, introduced in the early 1960s, proved a successful fishing method to catch deep burying flatfish, in particular sole. In less than 10 years, the otter trawl fleet was replaced by a highly specialised beam trawling fleet, despite an initial doubling of the loss rate of vessels due to stability problems. Engine power, size of the beam trawl, number of tickler chains and fishing speed rapidly increased and fishing activities expanded into previously lightly fished grounds and seasons. Following the ban on flatfish trawling within the 12 nautical mile zone for vessels of more than 300 hp in 1975 and with the restriction of engine power to 2000 hp in 1987, the beam trawl fleet bifurcated. Changes in the fleet capacity were related to the economic results and showed a cyclic pattern with a period of 6¿7 years. The arms race between fishers was fuelled by competitive interactions among fishers: while the catchability of the fleet more than doubled in the ten years following the introduction of the beam trawl, a decline in catchability was observed in reference beam trawlers that remained the same. Vessel performance was not only affected by the technological characteristics but also by the number and characteristics of competing vessels.
    Cross-sectoral long-term port and estuary visions
    Bracke, S. ; Bus, S. ; Chapuy, P. ; Dankers, N.M.J.A. ; Heijer, C. den; Kazer, S. ; Neumann, F. ; Poisson, N. ; Quemeneur, G. ; Sahin, F. ; Scott, C. ; Slootweg, H. ; Vanoutrive, T. ; Wit, M. de - \ 2007
    Rouen : Regional Directorate for the Environment of Haute Normandie - 49 p.
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