Effect of vitamin B12 and folic acid supplementation on bone mineral density and quantitative ultrasound parameters in older people with an elevated plasma homocysteine level: B-PROOF, a randomized controlled trial
Enneman, A.W. ; Swart, K.M.A. ; Wijngaarden, J.P. van; Dijk, S.C. van; Ham, A.C. ; Brouwer-Brolsma, E.M. ; Zwaluw, N.L. van der; Dhonukshe-Rutten, R.A.M. ; Cammen, T.J.M. van der; Groot, C.P.G.M. de; Meurs, J.B.J. van; Lips, P. ; Uitterlinden, A.G. ; Zillikens, M.C. ; Schoor, N.M. van; Velde, N. van der - \ 2015
Calcified Tissue International 96 (2015)5. - ISSN 0171-967X - p. 401 - 409.
placebo-controlled trial - postmenopausal women - fracture risk - turnover markers - elderly-women - metaanalysis - association - population - folate - bmd
High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged =65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p <0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement.
Development of a leafy Brassica rapa fixed line collection for genetic diversity and population structure analysis
Pang, W. ; Li, X. ; Choi, S.R. ; Dhandapani, V. ; Im, S. ; Park, M.Y. ; Jang, C.S. ; Yang, M.S. ; Ham, I.K. ; Lee, E.M. ; Kim, W. ; Lee, S.S. ; Bonnema, A.B. ; Park, S. ; Piao, Z. ; Lim, Y.P. - \ 2015
Molecular Breeding 35 (2015)1. - ISSN 1380-3743
genome sequencing project - microspore culture - linkage map - napus l. - microsatellite markers - repeat markers - construction - crop - association - centers
Brassica rapa is an economically important crop with a wide range of morphologies. Developing a set of fixed lines and understanding their diversity has been challenging, but facilitates resource conservation. We investigated the genetic diversity and population structure of 238 fixed lines of leafy B. rapa with 45 new simple sequence repeat markers and 109 new NGS (next-generation sequencing)-generated single nucleotide polymorphism markers evenly distributed throughout the B. rapa genome. Phylogenetic analysis classified the vegetable fixed lines into four subgroups, with the three oil types forming a separate and relatively distant cluster. A model-based population structure analysis identified four subpopulations corresponding to geographical origins and morphological traits, and revealed extensive allelic admixture. In particular, the Chinese cabbage cluster was subdivided into three groups and showed considerable correlation with leaf- and heading-related traits (leaf and heading shape). The vegetable B. rapa fixed lines successfully developed in our study could be valuable materials for establishing a multinational Brassica rapa diversity resource. Understanding the genetic diversity and population structure could be useful for utilization of the representative genetic variation and further genomic analysis.
Surfactant-polymer interactions: molecular architecture does matter
Banerjee, S. ; Cazeneuve, C. ; Baghdadli, N. ; Ringeissen, S. ; Leermakers, F.A.M. ; Luengo, G.S. - \ 2015
Soft Matter 11 (2015). - ISSN 1744-683X - p. 2504 - 2511.
block copolymer adsorption - nonionic surfactants - statistical thermodynamics - chain molecules - phase-behavior - simulation - interface - association - mixtures - water
Polymer–surfactant mixtures are found in many industrial formulations, and hence there is a significant interest in understanding, at a molecular level, how the self-assembly of surfactant is affected by oppositely-charged polyelectrolytes (PEs). We use self-consistent field modeling and show that the modes of interaction of PEs strongly depend on the architecture of the PE on the segmental level. Hydrophilic cationic PEs with their charge proximal to the linear backbone are expected to bind electrostatically to the outsides of the coronas of the spherical micelles of anionic surfactants, such as sodium laureth sulphate (SLES). As a result, the surfactant aggregation number increases, but at the same time the colloidal stability deteriorates, due to bridging of the PEs between micelles. PEs with their charge somewhat displaced from the backbone by way of short hydrophobic spacers, are expected to be present inside a micelle at the core–corona boundary. In this case the aggregation number decreases, yet the colloidal stability is retained. Hence, SLES tends to remove hydrophilic PEs from an aqueous solution, whereas it solubilizes more hydrophobic ones. The binding isotherm shows that the uptake of PEs remains typically below charge compensation and in this case the spherical micelle topology remains the preferred state.
Bayesian GWAS and network analysis revealed new candidate genes for number of teats in pigs
Verardo, L.L. ; Silva, F.F. ; Varona, L. ; Resende, R. ; Bastiaansen, J.W.M. ; Lopes, P.S. ; Guimaraes, S.E.F. - \ 2015
Journal of Applied Genetics 56 (2015)1. - ISSN 1234-1983 - p. 123 - 132.
quantitative trait loci - stress-syndrome gene - divergent crosses - messenger-rna - mixed models - r-package - association - snp - receptor - identification
The genetic improvement of reproductive traits such as the number of teats is essential to the success of the pig industry. As opposite to most SNP association studies that consider continuous phenotypes under Gaussian assumptions, this trait is characterized as a discrete variable, which could potentially follow other distributions, such as the Poisson. Therefore, in order to access the complexity of a counting random regression considering all SNPs simultaneously as covariate under a GWAS modeling, the Bayesian inference tools become necessary. Currently, another point that deserves to be highlighted in GWAS is the genetic dissection of complex phenotypes through candidate genes network derived from significant SNPs. We present a full Bayesian treatment of SNP association analysis for number of teats assuming alternatively Gaussian and Poisson distributions for this trait. Under this framework, significant SNP effects were identified by hypothesis tests using 95 % highest posterior density intervals. These SNPs were used to construct associated candidate genes network aiming to explain the genetic mechanism behind this reproductive trait. The Bayesian model comparisons based on deviance posterior distribution indicated the superiority of Gaussian model. In general, our results suggest the presence of 19 significant SNPs, which mapped 13 genes. Besides, we predicted gene interactions through networks that are consistent with the mammals known breast biology (e.g., development of prolactin receptor signaling, and cell proliferation), captured known regulation binding sites, and provided candidate genes for that trait (e.g., TINAGL1 and ICK).
Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A
Esterik, J.C. van; Vitins, A.P. ; Hodemaekers, H.M. ; Kamstra, J.H. ; Legler, J. ; Pennings, J.L.A. ; Steegenga, W.T. ; Lute, C. ; Jelinek, J. ; Issa, J.P. ; Dollé, M.E.T. ; Ven, L.T.M. van der - \ 2015
Toxicology Letters 232 (2015)1. - ISSN 0378-4274 - p. 293 - 300.
endocrine disruptors - disease - bpa - xenoestrogens - association - epigenetics - expression - nutrition - evolution - chemicals
Bisphenol A (BPA) is a compound released from plastics and other consumer products used in everyday life. BPA exposure early in fetal development is proposed to contribute to programming of chronic diseases like obesity and diabetes, by affecting DNA methylation levels. Previously, we showed that in utero and lactational exposure of C57BL/6JxFVB hybrid mice via maternal feed using a dose range of 0–3000 µg/kg body weight/day resulted in a sex-dependent altered metabolic phenotype in offspring at 23 weeks of age. The most univocal effects were observed in females, with reduced body weights and related metabolic effects associated with perinatal BPA exposure. To identify whether the effects of BPA in females are associated with changes in DNA methylation, this was analyzed in liver, which is important in energy homeostasis. Measurement of global DNA methylation did not show any changes. Genome-wide DNA methylation analysis at specific CpG sites in control and 3000 µg/kg body weight/day females with the digital restriction enzyme analysis of methylation (DREAM) assay revealed potential differences, that could, however, not be confirmed by bisulfite pyrosequencing. Overall, we demonstrated that the observed altered metabolic phenotype in female offspring after maternal exposure to BPA was not detectably associated with liver DNA methylation changes. Still, other tissues may be more informative.
Probabilistic networks of blood metabolites in healthy subjects as indicators of latent cardiovascular risk
Saccenti, E. ; Suarez Diez, M. ; Luchinat, C. ; Santucci, C. ; Tenori, L. - \ 2015
Journal of Proteome Research 14 (2015)2. - ISSN 1535-3893 - p. 1101 - 1111.
l-arginine supplementation - gene-coexpression network - insulin-resistance - metabolomic networks - disease - obesity - expression - cholesterol - association - validation
The complex nature of the mechanisms behind cardiovascular diseases prevents the detection of latent early risk conditions. Network representations are ideally suited to investigate the complex interconnections between the individual components of a biological system underlying complex diseases. Here we investigate the patterns of correlations of an array of 29 metabolites identified and quantified in the plasma of 864 healthy blood donors and use a systems biology approach to define metabolite probabilistic networks specific for low and high latent cardiovascular risk. We adapted methods based on the likelihood of correlation and methods from information theory and combined them with resampling techniques. Our results show that plasma metabolite networks can be defined that associate with latent cardiovascular disease risk. The analysis of the networks supports our previous finding of a possible association between cardiovascular risk and impaired mitochondrial activity and highlights post-translational modifications (glycosilation and oxidation) of lipoproteins as a possible target-mechanism for early detection of latent cardiovascular risk.
Genome-wide survey indicates involvement of loci on canine chromosomes 7 and 31 in patellar luxation in flat-coated retrievers
Lavrijsen, I.C.M. ; Leegwater, P.A.J. ; Wangdee, C. ; Steenbeek, F.G. van; Schwencke, M. ; Breur, G.J. ; Meutstege, F.J. ; Nijman, I.J. ; Cuppen, E. ; Heuven, H.C.M. ; Hazewinkel, H.A.W. - \ 2014
BMC Genetics 15 (2014). - ISSN 1471-2156
dogs - breed - frequency - association - enrichment
Background: Patellar luxation is an orthopedic disorder in which the patella moves out of its normal location within the femoral trochlea of the knee and it can lead to osteoarthritis, lameness, and pain. In dogs it is a heritable trait, with both environmental and genetic factors contributing to the phenotype. The prevalence of patellar luxation in the Dutch Flat-Coated Retriever population is 24%. In this study, we investigated the molecular genetics of the disorder in this population. Results: Genome-wide association analysis of 15,823 single nucleotide polymorphisms (SNPs) in 45 cases and 40 controls revealed that patellar luxation was significantly associated with a region on chromosome CFA07, and possibly with regions on CFA03, CFA31, and CFA36. The exons of the genes in these regions, 0.5 Mb combined, were analyzed further. These exons from 15 cases and a pooled sample from 15 controls were enriched using custom genomic hybridization arrays and analyzed by massive parallel DNA sequencing. In total 7257 variations were detected. Subsequently, a selection of 144 of these SNPs were genotyped in 95 Flat-Coated Retrievers. Nine SNPs, in eight genes on CFA07 and CFA31, were associated with patellar luxation (P <10(-4)). Genotyping of these SNPs in samples from a variety of breeds revealed that the disease-associated allele of one synonymous SNP in a pseudogene of FMO6 was unique to Flat-Coated Retrievers. Conclusion: Genome-wide association analysis followed by targeted DNA sequencing identified loci on chromosomes 7 and 31 as being involved in patellar luxation in the Flat-Coated Retriever breed.
Estimation of residual energy intake and its genetic background during the growing period in pigs
Shirali, M. ; Doeschl-Wilson, A. ; Duthie, C. ; Knap, P.W. ; Kanis, E. ; Arendonk, J.A.M. van; Roehe, R. - \ 2014
Livestock Science 168 (2014). - ISSN 1871-1413 - p. 17 - 25.
feed-intake - production traits - body-composition - nitrogen-excretion - chemical-analysis - yorkshire swine - growth - parameters - association - efficiency
The aims of this study were to (i) compare models estimating residual energy intake (REI) using either lean and fat tissue growth or their proxy traits (average daily gain (ADG) and backfat thickness (BF)); (ii) determine genetic characteristics of REI at different growth stages and the entire test period; and (iii) examine 9 genetic and phenotypic relationships of REI with other production traits. Data from 315 pigs of an F2 generation were used which originated from crossing Pietrain sires with a commercial crossbred dam population. Average daily protein (APD) and lipid deposition (ALD), as measurements of lean and fat tissue growth, were obtained using the deuterium dilution technique on live animals. During growth from 60 to 140 kg, REI was estimated using 4 different models for energy intake that included, besides other systematic effects, (1) ADG and BF; (2) APD and ALD; (3) and (4) incorporated the same covariables as the first two models, respectively, but pre-adjusted for systematic effects. Genetic parameters and estimated breeding values were obtained based on univariate animal models using REML analysis. Over the entire growing period, heritabilities of different REI using different models were all estimated at 0.44 and their genetic correlations were at unity. At different growth stages heritabilities for REI were greater ranging from 0.47 to 0.50. Genetic correlations between REI estimates at different stages of growth, obtained using genetic model 4, indicated that REI at 60 to 90 kg was non-significantly (P>0.05) associated with REI at 90–120 kg (0.32±0.29) and 120–140 kg (0.28±0.28), but REI of the latter growth stages showed a significant (P
Whole-genome sequence analysis reveals differences in population management and selection of European low-input pig breeds.
Herrero-Medrano, J. ; Megens, H.J.W.C. ; Groenen, M. ; Bosse, M. ; Pérez-Enciso, M. ; Crooijmans, R.P.M.A. - \ 2014
BMC Genomics 15 (2014). - ISSN 1471-2164 - 12 p.
quantitative trait loci - il-12 receptor beta-2 - genetic diversity - domestic pig - conservation - variants - scan - zinc-alpha-2-glycoprotein - microsatellite - association
Background - A major concern in conservation genetics is to maintain the genetic diversity of populations. Genetic variation in livestock species is threatened by the progressive marginalisation of local breeds in benefit of high-output pigs worldwide. We used high-density SNP and re-sequencing data to assess genetic diversity of local pig breeds from Europe. In addition, we re-sequenced pigs from commercial breeds to identify potential candidate mutations responsible for phenotypic divergence among these groups of breeds. Results - Our results point out some local breeds with low genetic diversity, whose genome shows a high proportion of regions of homozygosis (>50%) and that harbour a large number of potentially damaging mutations. We also observed a high correlation between genetic diversity estimates using high-density SNP data and Next Generation Sequencing data (r¿=¿0.96 at individual level). The study of non-synonymous SNPs that were fixed in commercial breeds and also in any local breed, but with different allele, revealed 99 non-synonymous SNPs affecting 65 genes. Candidate mutations that may underlie differences in the adaptation to the environment were exemplified by the genes AZGP1 and TAS2R40. We also observed that highly productive breeds may have lost advantageous genotypes within genes involve in immune response – e.g. IL12RB2 and STAB1–, probably as a result of strong artificial in the intensive production systems in pig. Conclusions - The high correlation between genetic diversity computed with the 60K SNP and whole genome re-sequence data indicates that the Porcine 60K SNP Beadchip provides reliable estimates of genomic diversity in European pig populations despite the expected bias. Moreover, this analysis gave insights for strategies to the genetic characterization of local breeds. The comparison between re-sequenced local pigs and re-sequenced commercial pigs made it possible to report candidate mutations to be responsible for phenotypic divergence among those groups of breeds. This study highlights the importance of low input breeds as a valuable genetic reservoir for the pig production industry. However, the high levels of ROHs, inbreeding and potentially damaging mutations emphasize the importance of the genetic characterization of local breeds to preserve their genomic variability.
Bovine Neonatal Pancytopenia is a heritable trait of the dam rather than the calf and correlates with the magnitude of vaccine induced maternal alloantibodies not the MHC haplotype
Benedictus, L. ; Otten, H.G. ; Schaik, G. van; Ginkel, G.J. ; Heuven, H.C.M. ; Nielen, M. ; Rutten, V.P.M.G. ; Koets, A.P. - \ 2014
Veterinary Research 45 (2014). - ISSN 0928-4249 - 13 p.
class-i genes - hemorrhagic diathesis - cattle - antibody - calves - bnp - association - responses - sequence - beta-2-microglobulin
Bovine Neonatal Pancytopenia (BNP), a bleeding syndrome of neonatal calves, is caused by alloantibodies absorbed from the colostrum of particular cows. A commercial BVD vaccine is the likely source of alloantigens eliciting BNP associated alloantibodies. We hypothesized that the rare occurrence of BNP in calves born to vaccinated dams could be associated with genetic differences within dams and calves. We found that the development of BNP within calves was a heritable trait for dams, not for calves and had a high heritability of 19%. To elucidate which genes play a role in the development of BNP we sequenced candidate genes and characterized BNP alloantibodies. Alloantigens present in the vaccine have to be presented to the dam’s immune system via MHC class II, however sequencing of DRB3 showed no differences in MHC class II haplotype between BNP and non-BNP dams. MHC class I, a highly polymorphic alloantigen, is an important target of BNP alloantibodies. Using a novel sequence based MHC class I typing method, we found no association of BNP with MHC class I haplotype distribution in dams or calves. Alloantibodies were detected in both vaccinated BNP and non-BNP dams and we found no differences in alloantibody characteristics between these groups, but alloantibody levels were significantly higher in BNP dams. We concluded that the development of BNP in calves is a heritable trait of the dam rather than the calf and genetic differences between BNP and non-BNP dams are likely due to genes controlling the quantitative alloantibody response following vaccination.
Predicting major outcomes in type 1 diabetes: a model development and validation study
Soedamah-Muthu, S.S. ; Vergouwe, Y. ; Costacou, T. ; Miller, R.G. ; Zgibor, J. ; Chaturvedi, N. ; Snell-Bergeon, J.K. ; Maahs, D.M. ; Rewers, M. ; Forsblom, C. ; Harjutsalo, V. ; Groop, P.H. ; Fuller, J.H. ; Moons, K.G.M. ; Orchard, T.J. - \ 2014
Diabetologia 57 (2014)11. - ISSN 0012-186X - p. 2304 - 2314.
coronary-heart-disease - eurodiab prospective complications - all-cause mortality - cardiovascular-disease - pittsburgh epidemiology - risk-factors - intensive treatment - iddm complications - metabolic syndrome - association
Aims/hypothesis Type 1 diabetes is associated with a higher risk of major vascular complications and death. A reliable method that predicted these outcomes early in the disease process would help in risk classification. We therefore developed such a prognostic model and quantified its performance in independent cohorts. Methods Data were analysed from 1,973 participants with type 1 diabetes followed for 7 years in the EURODIAB Prospective Complications Study. Strong prognostic factors for major outcomes were combined in a Weibull regression model. The performance of the model was tested in three different prospective cohorts: the Pittsburgh Epidemiology of Diabetes Complications study (EDC, n¿=¿554), the Finnish Diabetic Nephropathy study (FinnDiane, n¿=¿2,999) and the Coronary Artery Calcification in Type 1 Diabetes study (CACTI, n¿=¿580). Major outcomes included major CHD, stroke, end-stage renal failure, amputations, blindness and all-cause death. Results A total of 95 EURODIAB patients with type 1 diabetes developed major outcomes during follow-up. Prognostic factors were age, HbA1c, WHR, albumin/creatinine ratio and HDL-cholesterol level. The discriminative ability of the model was adequate, with a concordance statistic (C-statistic) of 0.74. Discrimination was similar or even better in the independent cohorts, the C-statistics being: EDC, 0.79; FinnDiane, 0.82; and CACTI, 0.73. Conclusions/interpretation Our prognostic model, which uses easily accessible clinical features can discriminate between type 1 diabetes patients who have a good or a poor prognosis. Such a prognostic model may be helpful in clinical practice and for risk stratification in clinical trials.
Colorectal cancer risk and dyslipidemia: a case-cohort study nested in an Italian multicentre cohort
Agnoli, C. ; Grioni, S. ; Sieri, S. ; Sacerdote, C. ; Vineis, P. ; Tumino, R. ; Giurdanella, M.C. ; Pala, V. ; Mattiello, A. ; Chiodini, P. ; Iacoviello, L. ; Curtis, A. de; Cattaneo, L. ; Duijnhoven, F.J.B. van - \ 2014
Cancer Epidemiology 38 (2014)2. - ISSN 1877-7821 - p. 144 - 151.
metabolic syndrome - serum-cholesterol - colon-cancer - lipoprotein levels - blood-cholesterol - glucose - triglyceride - association - nutrition - lipids
Background: Dyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers. Methods: We conducted a case-cohort study on participants recruited to four Italian EPIC centers (Turin, Varese, Naples, and Ragusa; 34,148 subjects). A random subcohort of 850 subjects was obtained and 286 colorectal cancer cases were diagnosed. Triglycerides, total and HDL cholesterol were determined in plasma samples obtained at baseline and stored at -196 degrees C; LDL cholesterol was calculated. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox regression models using the Prentice method. Results: The highest tertiles of total (HR 1.66, 95% CI 1.12-2.45) and LDL cholesterol (HR 1.87, 95% CI 1.27-2.76) were associated with increased colorectal cancer risk compared to lowest tertiles. Risks were greater for men than women, and for postmenopausal than premenopausal women. Highest tertiles of total and LDL cholesterol were also significantly associated with increased risks of colon cancer, distal colon cancer, and rectal cancer, but not proximal colon cancer. Conclusions: Our findings suggest that high levels of total and LDL cholesterol increase colorectal cancer risk, particularly in men and postmenopausal women. However additional studies are needed to clarify the role of plasma lipids in these cancers, particularly in view of the conflicting findings of previous studies. (C) 2014 Elsevier Ltd. All rights reserved.
Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort
Dossus, L. ; Boutron-Ruault, M.C. ; Kaaks, R. ; Gram, I.T. ; Vilier, A. ; Fervers, B. ; Manjer, J. ; Tjonneland, A. ; Olsen, A. ; Overvad, K. ; Chang-Claude, J. ; Boeing, H. ; Steffen, A. ; Trichopoulou, A. ; Lagiou, P. ; Sarantopoulou, M. ; Palli, D. ; Berrino, F. ; Tumino, R. ; Vineis, P. ; Mattiello, A. ; Bueno-de-Mesquita, H.B. ; Duijnhoven, F.J.B. van - \ 2014
International Journal of Cancer 134 (2014)8. - ISSN 0020-7136 - p. 1871 - 1888.
environmental tobacco-smoke - postmenopausal women - california teachers - 1st childbirth - never smokers - exposure - metaanalysis - association - carcinogens - reanalysis
Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05–1.28], 1.14 [1.04–1.25] and 1.10 [1.01–1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29–2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34–0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.
Indigenous chicken genetic resources in Kenya: their unique attributes and conservation options for improved use
Ngeno, K. ; Waaij, E.H. van der; Kahi, A.K. - \ 2014
Worlds Poultry Science Journal 70 (2014)1. - ISSN 0043-9339 - p. 173 - 184.
native fowl - temperature - association - disease
The indigenous chicken (Gallus gallus domesticus) genetic resources (IC) comprise more than 80% of the overall poultry population in rural villages despite their low productivity. However, a holistic approach that increases productivity without increasing production costs or leading to loss of biodiversity is presently limited. Conversely, in most developing countries, there is almost no organizational structure for breeding programmes for improving and conserving IC. These locally adapted IC can only be conserved in the most rational and sustainable way by ensuring that they are functional part of different production systems. Their conservation should be through utilisation if they are to be of any benefit to the poor rural households. This discussion focuses on five very relevant questions that need to be answered if the conservation of IC is to be effective and sustainable: What, why and how should we conserve, who are the stakeholders and what are their roles in conservation efforts?
A quantitative trait locus on Bos taurus autosome 17 explains a large proportion of the genetic variation in de novo synthesized milk fatty acids
Duchemin, S.I. ; Visker, M.H.P.W. ; Arendonk, J.A.M. van; Bovenhuis, H. - \ 2014
Journal of Dairy Science 97 (2014)11. - ISSN 0022-0302 - p. 7276 - 7285.
selection signatures - genotype imputation - dairy-cattle - protein - dgat1 - association - population - parameters - lactation - summer
A genomic region associated with milk fatty acid (FA) composition has been detected on Bos taurus autosome (BTA)17 based on 50,000 (50K) single nucleotide polymorphism (SNP) genotypes. The aim of our study was to fine-map BTA17 with imputed 777,000 (777K) SNP genotypes to identify candidate genes associated with milk FA composition. Phenotypes consisted of gas chromatography measurements of 14 FA based on winter and summer milk samples. Phenotypes and genotypes were available on 1,640 animals in winter milk, and on 1,581 animals in summer milk samples. Single-SNP analyses showed that several SNP in a region located between 29.0 and 34.0 Mbp were in strong association with C6:0, C8:0, and C10:0. This region was further characterized based on haplotypes. In summer milk samples, for example, these haplotypes explained almost 10% of the genetic variance in C6:0, 9% in C8:0, 3.5% in C10:0, 1.8% in C12:0, and 0.9% in C14:0. Two groups of haplotypes with distinct predicted effects could be defined, suggesting the presence of one causal variant. Predicted haplotype effects tended to increase from C6:0 to C14:0; however, the proportion of genetic variance explained by the haplotypes tended to decrease from C6:0 to C14:0. This is an indication that the quantitative trait locus (QTL) region is involved either in the elongation process or in early termination of de novo synthesized FA. Although many genes are present in this QTL region, most of these genes on BTA17 have not been characterized yet. The strongest association was found close to the progesterone receptor membrane component 2 (PGRMC2) gene, which has not yet been associated with milk FA composition. Therefore, no clear candidate gene associated with milk FA composition could be identified for this QTL.
Phosphorylation of as1-casein is regulated by different genes
Bijl, E. ; Valenberg, H.J.F. van; Huppertz, T. ; Hooijdonk, A.C.M. van; Bovenhuis, H. - \ 2014
Journal of Dairy Science 97 (2014)11. - ISSN 0022-0302 - p. 7240 - 7246.
milk protein-composition - mammary-gland - dairy-cattle - casein kinase - bovine-milk - association - dgat1 - polymorphism - specificity - cows
Casein phosphorylation is a posttranslational modification catalyzed by kinase enzymes that attach phosphate groups to specific AA in the protein sequence. This modification is one of the key factors responsible for the stabilization of calcium phosphate nanoclusters in casein micelles and for the internal structure of the casein micelles. aS1-Casein (as1-CN) is of special interest because it constitutes up to 40% of the total casein fraction in milk, and it has 2 common phosphorylation states, with 8 (aS1-CN-8P) and 9 (aS1-CN-9P) phosphorylated serine residues. Factors affecting this variation in the degree of phosphorylation are not currently known. The objective of this research was to determine the genetic background of aS1-CN-8P and aS1-CN-9P. The genetic and phenotypic correlation between aS1-CN-8P and aS1-CN-9P was low (0.18 and 0.19, respectively). This low genetic correlation suggests a different genetic background. These differences were further investigated by means of a genome-wide association study, which showed that both aS1-CN-8P and aS1-CN-9P were affected by a region on Bos taurus autosome (BTA) 6, but only aS1-CN-8P was affected by a region on BTA11 that contains the gene that encodes for ß-lactoglobulin (ß-LG), and only aS1-CN-9P was affected by a region on BTA14 that contains the diacylglycerol acyltransferase 1 (DGAT1) gene. Estimated effects of ß-LG protein genotypes showed that only aS1-CN-8P was associated with the ß-LG A/B polymorphism (g.1772G>A and g.3054C>T); the AA genotype of ß-LG was associated with a lower concentration of aS1-CN-8P (-0.32% wt/wt) than the BB genotype (+0.41% wt/wt). Estimated effects of DGAT1 K232A genotypes showed that only aS1-CN-9P was associated with the DGAT1 gene polymorphism; DGAT1 AA genotype was associated with a higher aS1-CN-9P concentration (+0.53% wt/wt) than the DGAT1 KK genotype (-0.44% wt/wt). The results give insight in phosphorylation of aS1-CN-8P and aS1-CN-9P, which seem to be regulated by a different set of genes.
Effect of moderate alcohol consumption on fetuin-A levels in men and women: post-hoc analyses of three open-label randomized crossover trials
Joosten, M.M. ; Schrieks, I.C. ; Hendriks, H.F.J. - \ 2014
Diabetology & Metabolic Syndrome 6 (2014). - ISSN 1758-5996 - 5 p.
community-dwelling adults - insulin-resistance - cardiovascular-disease - rancho bernardo - older-adults - risk - association - metaanalysis - expression - biomarkers
Background Fetuin-A, a liver-derived glycoprotein that impairs insulin-signalling, has emerged as a biomarker for diabetes risk. Although moderate alcohol consumption has been inversely associated with fetuin-A, data from clinical trials are lacking. Thus, we evaluated whether moderate alcohol consumption decreases circulating levels of fetuin-A. Methods We analyzed data of three separate open-label, randomized, crossover trials: 1) 36 postmenopausal women consuming 250 ml white wine (25 g alcohol) or white grape juice daily for 6 weeks, 2) 24 premenopausal women consuming 660 ml beer (26 g alcohol) or alcohol-free beer daily for 3 weeks, and 3) 24 young men consuming 100 ml vodka (30 g alcohol) orange juice or only orange juice daily for 4 weeks. After each treatment period fasting blood samples were collected. Results Circulating fetuin-A concentrations decreased in men after vodka consumption (Mean¿±¿SEM: 441¿±¿11 to 426¿±¿11 µg/ml, p¿=¿0.02), but not in women after wine (448¿±¿17 to 437¿±¿17 µg/ml, p¿=¿0.16) or beer consumption (498¿±¿15 to 492¿±¿15 µg/ml, p¿=¿0.48) compared to levels after each corresponding alcohol-free treatment. Post-hoc power analyses indicated that the statistical power to detect a similar effect as observed in men was 30% among the postmenopausal women and 31% among the premenopausal women. Conclusions In these randomized crossover trials, moderate alcohol consumption decreased fetuin-A in men but not in women. This sex-specific effect may be explained by the relatively short intervention periods or the low statistical power in the trials among women.
Screen time, adiposity and cardiometabolic markers: mediation by physical activity, not snacking, among 11-year-old children
Berendtzen, N.E. ; Smit, H.A. ; Rossem, L. van; Gehring, U. ; Kerkhof, M. van de; Postma, D.S. ; Boshuizen, H.C. - \ 2014
International Journal of Obesity 38 (2014). - ISSN 0307-0565 - p. 1317 - 1323.
body-mass index - sedentary behavior - risk-factors - computer use - television - obesity - health - youth - association - adolescents
Background:There is evidence for a relation of TV viewing with adiposity and increased cardiometabolic risk factors in children and adolescents. It is unclear to what extent this relation is mediated by snacking and lack of physical activity. We determined whether associations of screen time with adiposity and cardiometabolic markers were mediated by these behaviours.Methods:Children from a population-representative Dutch birth cohort (n=1447) reported screen time and other lifestyle factors by a questionnaire around the age of 11 years (range 10-14) and had anthropometry and cardiometabolic markers measured around the age of 12 years (range 12-14). Adjusted associations of screen time with snacking, physical activity, adiposity and cardiometabolic markers (total-to-high-density lipoprotein cholesterol (TC/HDLC) ratio, blood pressure, glycated haemoglobin) were assessed by using formal mediation analysis. We tested the hypothesized paths by structural equation modeling, which allows quantification of the indirect effects associated with potential mediators.Results:Children with ¿20¿h screen time per week consumed more snacks (1.9 vs 1.3 portions per day) and were less physically active (4.3 vs 4.8 days per week) than children with maximum 6¿h screen time. Screen time was directly associated with higher adiposity (standardized ß=0.10-0.12 depending on the outcome, P
Role of the Goat K222-PrPC Polymorphic variant in Prion Infection Resistance
Aguilar-Calvo, P. ; Espinosa, J.C. ; Pintado, B. ; Gutiérrez-Adán, A. ; Alamilo, E. ; Miranda, A. ; Prieto, I. ; Bossers, A. ; Andreoletti, O. ; Torres, J.M. - \ 2014
Journal of Virology 88 (2014)5. - ISSN 0022-538X - p. 2670 - 2676.
bovine spongiform encephalopathy - protein gene polymorphisms - caprine prp gene - natural scrapie - classical scrapie - transgenic mice - sheep - identification - association - genotype
The prion protein-encoding gene (prnp) strongly influences the susceptibility of small ruminants to transmissible spongiform encephalopathies (TSEs). Hence, selective breeding programs have been implemented to increase sheep resistance to scrapie. For goats, epidemiological and experimental studies have provided some association between certain polymorphisms of the cellular prion protein (PrPC) and resistance to TSEs. Among them, the Q/K polymorphism at PrPC codon 222 (Q/K222) yielded the most promising results. In this work, we investigated the individual effects of the K222-PrPC variant on the resistance/susceptibility of goats to TSEs. For that purpose, we generated two transgenic mouse lines, expressing either the Q222 (wild type) or K222 variant of goat PrPC. Both mouse lines were challenged intracerebrally with a panel of TSE isolates. Transgenic mice expressing the wild-type (Q222) allele were fully susceptible to infection with all tested isolates, whereas transgenic mice expressing similar levels of the K222 allele were resistant to all goat scrapie and cattle BSE isolates but not to goat BSE isolates. Finally, heterozygous K/Q222 mice displayed a reduced susceptibility to the tested panel of scrapie isolates. These results demonstrate a highly protective effect of the K222 variant against a broad panel of different prion isolates and further reinforce the argument supporting the use of this variant in breeding programs to control TSEs in goat herds. IMPORTANCE The objective of this study was to determine the role of the K222 variant of the prion protein (PrP) in the susceptibility/resistance of goats to transmissible spongiform encephalopathies (TSEs). Results showed that transgenic mice expressing the goat K222-PrP polymorphic variant are resistant to scrapie and bovine spongiform encephalopathy (BSE) agents. This protective effect was also observed in heterozygous Q/K222 animals. Therefore, the single amino acid exchange from Q to K at codon 222 of the cellular prion protein provides resistance against TSEs. All the results presented here support the view that the K222 polymorphic variant is a good candidate for selective breeding programs to control and eradicate scrapie in goat herds.
No role for vitamin D or a moderate fat diet in aging induced cognitive decline and emotional reactivity in C57BL/6 mice
Brouwer, E.M. ; Schuurman, T. ; Groot, C.P.G.M. de; Feskens, E.J.M. ; Lute, C. ; Naninck, E.F.G. ; Arndt, S.S. ; Staay, F.J. van der; Bravenboer, N. ; Korosi, A. ; Steegenga, W.T. - \ 2014
Behavioural Brain Research 267 (2014). - ISSN 0166-4328 - p. 133 - 143.
serum 25-hydroxyvitamin d - d supplementation - d deficiency - depressive symptoms - alzheimers-disease - insulin-resistance - older women - pre-post - brain - association
Background Epidemiological studies have shown associations between vitamin D, mental health and glucose homeostasis in the elderly. Causal evidence, however, is still lacking. Objective The objective of this study was to investigate the importance of vitamin D in the prevention of emotional disturbances and cognitive decline in aging C57BL/6 mice, with pre-diabetes type II as potential effect modifier. Methods Mice were exposed to one of four diets from 10 months till 24 months of age: low fat vitamin D adequate (LFD), LF vitamin D deficient (LF), moderate fat vitamin D adequate (MFD), and MF vitamin D deficient (MF). The MFD/MF diet was applied to induce a condition resembling pre-diabetes type II. Behavior was assessed twice in the same group of mice at 6–8 and at 22–23 months of age using the Open Field Test (OFT), Elevated Plus Maze (EPM), Object Recognition Test (ORT) and the Morris Water Maze (MWM). Results We successfully induced vitamin D deficiency in the LF/MF mice. Moreover, fasting glucose and fasting insulin levels were significantly higher in MFD/MF mice than in LFD/LF mice. A significant aging effect was observed for most behavioral parameters. A MF(D) diet was shown to delay or prevent the age-related increase in emotional reactivity in the EPM. No effect of vitamin D or vitamin D*fat on behavioral outcomes was measured. Conclusion Aging significantly affected emotional reactivity and cognitive performance. Although other studies have shown effects of vitamin D on emotional reactivity and cognitive performance in mice, these findings could not be confirmed in aged C57BL/6 mice in this study.