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Search Results: 1 - 10 of 200776 matches for " P. Eline Slagboom "
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Association between Several Clinical and Radiological Determinants with Long-Term Clinical Progression and Good Prognosis of Lower Limb Osteoarthritis
Erlangga Yusuf, Jessica Bijsterbosch, P. Eline Slagboom, Herman M. Kroon, Frits R. Rosendaal, Tom W. J. Huizinga, Margreet Kloppenburg
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025426
Abstract: Objective To investigate the factors associated with clinical progression and good prognosis in patients with lower limb osteoarthritis (OA). Methods Cohort study of 145 patients with OA in either knee, hip or both. Progression was defined as 1) new joint prosthesis or 2) increase in WOMAC pain or function score during 6-years follow-up above pre-defined thresholds. Patients without progression with decrease in WOMAC pain or function score lower than pre-defined thresholds were categorized as good prognosis. Relative risks (RRs) for progression and good prognosis with 95% confidence interval (95% CI) were calculated by comparing the highest tertile or category to the lowest tertile, for baseline determinants (age, sex, BMI, WOMAC pain and function scores, pain on physical examination, total range of motion (tROM), osteophytes and joint space narrowing (JSN) scores), and for worsening in WOMAC pain and function score in 1-year. Adjustments were performed for age, sex, and BMI. Results Follow-up was completed by 117 patients (81%, median age 60 years, 84% female); 62 (53%) and 31 patients (26%) showed progression and good prognosis, respectively. These following determinants were associated with progression: pain on physical examination (RR 1.2 (1.0 to 1.5)); tROM (1.4 (1.1 to 1.6); worsening in WOMAC pain (1.9 (1.2 to 2.3)); worsening in WOMAC function (2.4 (1.7 to 2.6)); osteophytes 1.5 (1.0 to 1.8); and JSN scores (2.3 (1.5 to 2.7)). Worsening in WOMAC pain (0.1 (0.1 to 0.8)) and function score (0.1 (0.1 to 0.7)), were negatively associated with good prognosis. Conclusion Worsening of self-reported pain and function in one year, limited tROM and higher osteophytes and JSN scores were associated with clinical progression. Worsening in WOMAC pain and function score in 1- year were associated with lower risk to have good prognosis. These findings help to inform patients with regard to their OA prognosis.
Periconceptional Maternal Folic Acid Use of 400 μg per Day Is Related to Increased Methylation of the IGF2 Gene in the Very Young Child
Régine P. Steegers-Theunissen,Sylvia A. Obermann-Borst,Dennis Kremer,Jan Lindemans,Cissy Siebel,Eric A. Steegers,P. Eline Slagboom,Bastiaan T. Heijmans
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007845
Abstract: Countries worldwide recommend women planning pregnancy to use daily 400 μg of synthetic folic acid in the periconceptional period to prevent birth defects in children. The underlying mechanisms of this preventive effect are not clear, however, epigenetic modulation of growth processes by folic acid is hypothesized. Here, we investigated whether periconceptional maternal folic acid use and markers of global DNA methylation potential (S-adenosylmethionine and S-adenosylhomocysteine blood levels) in mothers and children affect methylation of the insulin-like growth factor 2 gene differentially methylation region (IGF2 DMR) in the child. Moreover, we tested whether the methylation of the IGF2 DMR was independently associated with birth weight.
Association of Liver Enzymes and Computed Tomography Markers of Liver Steatosis with Familial Longevity
Michiel Sala, Lucia J. M. Kroft, Boudewijn R?ell, Jeroen van der Grond, P. Eline Slagboom, Simon P. Mooijaart, Albert de Roos, Diana van Heemst
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091085
Abstract: Objective Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT). Research Design and Methods: We measured nonfasting alanine transaminase (ALT), aspartate aminotransferase (AST), and Υ-glutamyl transferase (GGT) in 1625 subjects (736 men, mean age 59.1 years) from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230) were evaluated and CT was performed (n = 268) for assessment of liver-spleen (L/S) ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD). Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. Results Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03), while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively). Conclusions Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver steatosis is similar between offspring of long-lived siblings and control subjects.
Systematic Testing of Literature Reported Genetic Variation Associated with Coronary Restenosis: Results of the GENDER Study
Jeffrey J. W. Verschuren, Stella Trompet, Iris Postmus, M. Lourdes Sampietro, Bastiaan T. Heijmans, Jeanine J. Houwing-Duistermaat, P. Eline Slagboom, J. Wouter Jukema
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042401
Abstract: Background Coronary restenosis after percutaneous coronary intervention still remains a significant problem, despite all medical advances. Unraveling the mechanisms leading to restenosis development remains challenging. Many studies have identified genetic markers associated with restenosis, but consistent replication of the reported markers is scarce. The aim of the current study was to analyze the joined effect of previously in literature reported candidate genes for restenosis in the GENetic DEterminants of Restenosis (GENDER) databank. Methodology/Principal Findings Candidate genes were selected using a MEDLINE search including the terms ‘genetic polymorphism’ and ‘coronary restenosis’. The final set included 36 genes. Subsequently, all single nucleotide polymorphisms (SNPs) in the genomic region of these genes were analyzed in GENDER using set-based analysis in PLINK. The GENDER databank contains genotypic data of 2,571,586 SNPs of 295 cases with restenosis and 571 matched controls. The set, including all 36 literature reported genes, was, indeed, significantly associated with restenosis, p = 0.024 in the GENDER study. Subsequent analyses of the individual genes demonstrated that the observed association of the complete set was determined by 6 of the 36 genes. Conclusion Despite overt inconsistencies in literature, with regard to individual candidate gene studies, this is the first study demonstrating that the joint effect of all these genes together, indeed, is associated with restenosis.
Prenatal Famine and Genetic Variation Are Independently and Additively Associated with DNA Methylation at Regulatory Loci within IGF2/H19
Elmar W. Tobi, P. Eline Slagboom, Jenny van Dongen, Dennis Kremer, Aryeh D. Stein, Hein Putter, Bastiaan T. Heijmans, L. H. Lumey
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037933
Abstract: Both the early environment and genetic variation may affect DNA methylation, which is one of the major molecular marks of the epigenome. The combined effect of these factors on a well-defined locus has not been studied to date. We evaluated the association of periconceptional exposure to the Dutch Famine of 1944–45, as an example of an early environmental exposure, and single nucleotide polymorphisms covering the genetic variation (tagging SNPs) with DNA methylation at the imprinted IGF2/H19 region, a model for an epigenetically regulated genomic region. DNA methylation was measured at five differentially methylated regions (DMRs) that regulate the imprinted status of the IGF2/H19 region. Small but consistent differences in DNA methylation were observed comparing 60 individuals with periconceptional famine exposure with unexposed same-sex siblings at all IGF2 DMRs (PBH<0.05 after adjustment for multiple testing), but not at the H19 DMR. IGF2 DMR0 methylation was associated with IGF2 SNP rs2239681 (PBH = 0.027) and INS promoter methylation with INS SNPs, including rs689, which tags the INS VNTR, suggesting a mechanism for the reported effect of the VNTR on INS expression (PBH = 3.4×10?3). Prenatal famine and genetic variation showed similar associations with IGF2/H19 methylation and their contributions were additive. They were small in absolute terms (<3%), but on average 0.5 standard deviations relative to the variation in the population. Our analyses suggest that environmental and genetic factors could have independent and additive similarly sized effects on DNA methylation at the same regulatory site.
Familial Longevity Is Marked by Better Cognitive Performance at Middle Age: The Leiden Longevity Study
Marjon Stijntjes, Anton J. M. de Craen, Diana van Heemst, Carel G. M. Meskers, Mark A. van Buchem, Rudi G. J. Westendorp, P. Eline Slagboom, Andrea B. Maier
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057962
Abstract: Background Decline in cognitive performance is a highly prevalent health condition in elderly. We studied whether offspring of nonagenarian siblings with a familial history of longevity, perform better on cognitive tests compared to their partners as controls. This is relevant since it could provide insights into determinants underlying decline in cognitive performance. Methods Cross-sectional analysis within the longitudinal cohort of the Leiden Longevity Study consisting of middle-aged offspring of nonagenarian siblings together with their partners (n = 500, mean age (SD) 66.3 (6.1) and 65.7 (7.2) years, respectively) as controls. Memory function, attention and processing speed were tested using the 15-Picture Learning Test, Stroop test and Digit Symbol Substitution Test. Data were analyzed with regression adjusted for age, gender, years of education and additionally for diabetes mellitus, cardiovascular diseases, alcohol use, smoking, inflammatory markers and apolipoprotein E genotype. Robust standard errors were used to account for familial relationships among the offspring. Results Cognitive performance was worse at higher calendar age (p<0.001, all except Stroop test part 1). The offspring performed better compared to their partners on trial 3 (p = 0.005), the immediate (p = 0.016) and delayed (p = 0.004) recall of the 15-Picture Learning Test as well as on the interference and combined interference score of the Stroop test (p = 0.014 and p = 0.036, respectively) in the fully adjusted model. The difference between offspring and partners was estimated to be more than three years according to the observed difference in calendar age. Conclusions Offspring of nonagenarian siblings with a familial history of longevity have better cognitive performance compared to the group of their partners of comparable age. This effect is independent of age-related diseases and known possible confounders. Possible explanations might be differences in subclinical vascular pathology between both groups.
ApoE Plasma Levels and Risk of Cardiovascular Mortality in Old Age
Simon P Mooijaart ,Jimmy F. P Berbée,Diana van Heemst,Louis M Havekes,Anton J. M de Craen,P. Eline Slagboom,Patrick C. N Rensen,Rudi G. J Westendorp
PLOS Medicine , 2006, DOI: 10.1371/journal.pmed.0030176
Abstract: Background The ε2, ε3, and ε4 alleles of the apolipoprotein E gene (APOE) encode three isoforms, apoE2, E3, and E4, respectively. The apoE isoforms circulate in different plasma concentrations, but plasma concentrations of the same isoform also differ between individuals. Whereas the isoforms have been associated with cardiovascular disease, the relation between plasma apoE levels and cardiovascular disease is unknown. Methods and Findings We assessed APOE genotypes, plasma levels of apoE, cardiovascular risk factors, and mortality in a population-based sample of 546 individuals aged 85 y who participated in the Leiden 85-plus Study and were prospectively followed for specific causes of death for 5 y. Participants in the highest tertile of apoE levels suffered a twofold-increased risk of cardiovascular mortality (hazard ratio compared to lowest tertile, 2.08; 95% confidence interval [CI], 1.30 to 3.33). Among the 324 participants with the ε3ε3 genotype, the hazard from cardiovascular disease was threefold increased (highest versus lowest tertile 3.01; 95% CI 1.60 to 5.66), with similar estimates for men and women. Other causes of death were not increased significantly. Plasma levels of apoE in ε3ε3 participants were positively correlated with total cholesterol ( p < 0.001), low-density lipoprotein cholesterol ( p < 0.001) and triglycerides ( p < 0.001) and negatively with high-density lipoprotein cholesterol levels ( p = 0.010). Adjustment for plasma lipids did not change the hazard ratios, whereas interaction was absent. The risk associated with high levels of apoE, however, was strongest in participants from the lowest tertile of C-reactive protein (CRP) levels and absent in those from the highest tertile ( pinteraction < 0.001). Among participants from the lowest tertile of CRP levels, those with a high apoE levels had a significantly steeper increase in CRP than those with low apoE levels ( p = 0.020). Similar cardiovascular mortality risks as in ε3ε3 participants were found in ε2 and ε4 carriers. Conclusions In old age, high plasma apoE levels precede an increase of circulating CRP and strongly associates with cardiovascular mortality, independent of APOE genotype and plasma lipids.
Homocysteine and Familial Longevity: The Leiden Longevity Study
Carolien A. Wijsman,Diana van Heemst,Maarten P. Rozing,P. Eline Slagboom,Marian Beekman,Anton J. M. de Craen,Andrea B. Maier,Rudi G. J. Westendorp,Henk J. Blom,Simon P. Mooijaart
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017543
Abstract: Homocysteine concentrations are a read-out of methionine metabolism and have been related to changes in lifespan in animal models. In humans, high homocysteine concentrations are an important predictor of age related disease. We aimed to explore the association of homocysteine with familial longevity by testing whether homocysteine is lower in individuals that are genetically enriched for longevity. We measured concentrations of total homocysteine in 1907 subjects from the Leiden Longevity Study consisting of 1309 offspring of nonagenarian siblings, who are enriched with familial factors promoting longevity, and 598 partners thereof as population controls. We found that homocysteine was related to age, creatinine, folate, vitamin B levels and medical history of hypertension and stroke in both groups (all p<0.001). However, levels of homocysteine did not differ between offspring enriched for longevity and their partners, and no differences in the age-related rise in homocysteine levels were found between groups (p for interaction 0.63). The results suggest that homocysteine metabolism is not likely to predict familial longevity.
Decreased Levels of Bisecting GlcNAc Glycoforms of IgG Are Associated with Human Longevity
L. Renee Ruhaak,Hae-Won Uh,Marian Beekman,Carolien A. M. Koeleman,Cornelis H. Hokke,Rudi G. J. Westendorp,Manfred Wuhrer,Jeanine J. Houwing-Duistermaat,P. Eline Slagboom,André M. Deelder
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012566
Abstract: Markers for longevity that reflect the health condition and predict healthy aging are extremely scarce. Such markers are, however, valuable in aging research. It has been shown previously that the N-glycosylation pattern of human immunoglobulin G (IgG) is age-dependent. Here we investigate whether N-linked glycans reflect early features of human longevity.
Selection for Genetic Variation Inducing Pro-Inflammatory Responses under Adverse Environmental Conditions in a Ghanaian Population
Maris Kuningas,Linda May,Riin Tamm,David van Bodegom,Anita H. J. van den Biggelaar,Johannes J. Meij,Marijke Fr?lich,Juventus B. Ziem,Helena E. D. Suchiman,Andres Metspalu,P. Eline Slagboom,Rudi G. J. Westendorp
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007795
Abstract: Chronic inflammation is involved in the pathogenesis of chronic age-associated, degenerative diseases. Pro-inflammatory host responses that are deleterious later in life may originate from evolutionary selection for genetic variation mediating resistance to infectious diseases under adverse environmental conditions.
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