Albert Hofman

..The Generation R Study provides unique possibilities to examine effects of short- and long-term air pollution exposure on various maternal and childhood outcomes and to identify potential critical windows of exposure...

..The considerable traffic-related intra-urban spatial variation needs to be considered in exposure assessment. Residential proximity to traffic is a proxy for traffic-related exposures that takes into account within-city contrasts...

..Early detection and counselling is expected to reduce the prevalence of asthma symptoms and improve health-related quality of life at age 6 years...

..The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis...

..The objective of this study was to examine whether T2D gene polymorphism TCF7L2 rs7903146 is associated with growth patterns from fetal life until infancy...

..To develop a prediction model that predicts disability in community-dwelling older people. Insight in the predictors of disability is needed to target preventive strategies for people at increased risk...

..epib.nl/rotterdamstudy). This article gives the reasons for the study and its design. It also presents a summary of the major findings and an update of the objectives and methods...

..Perhaps the most important message from the Rotterdam Study is the great potential for prevention or postponement of neurological diseases in elderly people. The time for preventive nihilism is over...

..The study entered its pilot phase to test the logistics in December 2001. Full participant recruitment and complete data collection started in 2002...

..erasmus-epidemiology.nl/rotterdamstudy ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods...

..epib.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods...

..Vascular pathology was not significantly associated with ACE. This suggests a modest but significant increase in risk of AD and early AD pathology in women homozygous for the ACE I-allele independent of vascular factors...

..We investigated whether unrecognized MI is also a risk factor for dementia and cerebral small vessel disease (white matter lesions and brain infarction) in 2 population-based cohort studies...

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..Our findings suggest that genetic variation in the renin-angiotensin system may play a role in determining carotid distensibility and pulse pressure...

..Eventually, results forthcoming from the Generation R Study contribute to the development of strategies for optimizing health and healthcare for pregnant women and children...

..1 to 16.5) to develop MI compared with the reference group. In conclusion, this population-based study suggests that the combined presence of unfavorable CFH and CRP genetic profiles is associated with risk of MI...

..04) in the risk of retinopathy was observed compared with participants with the wild-type genotype. In conclusion, our findings suggest that this IGF-I gene polymorphism is associated with an increased risk of diabetic retinopathy...

..Possible effect modification by smoking and inflammatory markers was examined...

..CRP levels were associated with pulse wave velocity (p = 0.007). In conclusion, the interleukin-6-174 G/C polymorphism is associated with increased arterial stiffness and pulse pressure...

..31), 1.06 (0.99-1.14), and 1.20 (1.10-1.31). CONCLUSION: The results of this study suggest that, in a population of apparently healthy older adults, PP is not a better predictor of cardiovascular events and all-cause mortality than SBP...

..5; 95% CI, 1.1-2.0) of fragility fracture in women (n = 4212) but not in men (n = 2799). An approximation of hip bone geometry (from DXA) suggested the polymorphism is associated with bone strength and stability in gender-specific ways...

..5 cm shorter per allele copy of the ESR1 haplotype 1 (P for trend = 0.03). In conclusion, we demonstrate a role for genetic variations in the estrogen receptor alpha gene in determining adult stature in women...

..We sought to examine the associations of maternal C-reactive protein (CRP) levels with fetal growth and the risks of neonatal complications...

..These results suggest that differences in infant neuromotor development, a marker of behavioral and cognitive problems, are at least partly caused by processes occurring early in fetal life...

..We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women...

..ACE-inhibitor users with at least one copy of the 235T-allele of the AGT gene might have an increased risk of MI and stroke...

..Associations for NR4A2 were found with both HDL levels and blood pressure. It remains to be investigated which pathophysiological mechanisms pertain to NR4A2 function in cardiovascular disease...

..Relative to extensive metabolizers, these poor metabolizers may have lower baseline serotonin concentrations in various brain regions, and may be more prone to depression or anxiety...

..87 (95% CI 0.64-1.19) for vitamin A and 0.94 (95% CI 0.60-1.48) for vitamin E. Antioxidants were not related to CD in non-demented subjects. Our findings suggest no association between plasma levels of vitamin A and E and AD or CD...

..Interaction of ESR2 with ESR1 and IGF1 was determined and revealed a deleterious genetic combination that enhances the risk of osteoporotic fracture...

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..The effect of the cholesteryl ester transfer protein (CETP) I405V polymorphism on lipid levels, atherosclerosis and myocardial infarction (MI) was examined in 6421 participants from the Rotterdam Study...

..This study was performed to determine to what extent variants within established genes (MYOC, OPTN, and WDR36) and newly identified common genetic variants (ATOH7, CDKN2B, and SIX1) contribute to the risk of OAG...

..8, 95% CI 1.1-2.8) and current smokers (HR = 3.1, 95% CI 1.4-7.1), but not in former smokers (HR = 1.3, 95% CI 0.7-2.4). HFE mutations are associated with increased risk of incident CHD in women...

..In conclusion, fibrinogen FGG and FGA gene haplotypes are not associated with coronary events, coronary atherosclerosis or extracoronary atherosclerosis. Confirmation of these findings by future population-based studies is warranted...

..Measures reflecting white matter microstructural integrity may provide additional information to investigate the relation between white matter changes and cognition...

..Geometric mean levels of CRP increased with the total number of sites showing progression of atherosclerosis (P=0.002 for trend). CONCLUSIONS: CRP predicts progression of atherosclerosis measured at various sites in the arterial tree...

..Correction of niacin deficiency and SIRT1 modulators may prolong the life span of patients with diabetes...

..69, P = 0.23; joint HR = 0.60, P = 0.0018). In conclusion, this study provided additional evidence for association between genetic variation within NOS1AP and SCD. The mechanism by which this effect is exerted remains to be elucidated...

..Since serum levels of C-reactive protein are partly determined by genetic factors, we examined the association between genetic variation in the C-reactive protein gene with dementia and AD...

..We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis...

..This study was designed to investigate the association between a common polymorphism (Tyr402His, rs1061170) in the complement factor H (CFH) gene and risk of coronary heart disease...

..05). These findings emphasize the potential effect of prenatal gene-environment interaction, and give insight in possible mechanisms accounting for children's individual vulnerability to develop emotional and behavioral problems...

..The aim of this study was to determine whether common carotid IMT in addition to traditional risk factors improves risk classification in a general population of older people...

..To conclude, low adherence to a Mediterranean diet in early pregnancy seems associated with decreased intra-uterine size with a lower placental and a lower birth weight...

..The mechanisms underlying venular dilatation deserve more attention, as they may provide new clues into the pathophysiology of cerebral small vessel disease...

..Recent case-control studies demonstrated an association between the complement factor H (CFH) gene, a regulator of complement, and AMD...

..We investigated whether NSAIDs were associated with overanticoagulation during therapy with coumarins and evaluated the effect of the CYP2C9 polymorphisms on this potential interaction...

..Therefore, we investigated whether this common genetic polymorphism influenced dose requirements and effects of coumarin anticoagulants...

..To study whether NOS1AP single nucleotide polymorphisms (SNPs), rs10494366 T>G and rs10918594 C>G, modify the heart-rate-corrected QT (QTc) prolonging effect of calcium channel blockers...

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..To investigate whether polymorphisms in the estrogen receptor alpha (ESR1) and beta (ESR2) genes were a risk factor for open-angle glaucoma (OAG)...

..The aim of this paper is to examine the association between the AGT M235T polymorphism and symptoms of depression in two independent populations; a population-based study, and a family-based study...

..In our analysis, the haplotype tagged by the G allele of SNP rs2069442 was significantly associated with AD (p = 0.05). In conclusion, our study suggests that CDK5 may be associated with AD...

..05). All associations were independent of age and gender. Our study demonstrated that the genetic effect of the DBP gene on fracture risk appears only in combination with other genetic and environmental risk factors for bone metabolism...

..Remarkably, it is absent in the aorta and the lower-extremity vessels. Factors causing this site-specific gender difference require further investigation...

..The aim of this study was to examine whether C-reactive protein (CRP) levels and CRP gene variations were associated with an altered risk of colorectal, lung, breast, or prostate cancer...

..There was no relation between serum levels of cortisol and the risk of developing dementia or Alzheimer's disease. These results suggest that that morning serum cortisol is not a causal factor in the development of dementia...

..We therefore investigated 5 polymorphisms in the TGF-beta1 gene (-800 G/A, -509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro, and codon 263 Thr/Ile) in relation to the risk of myocardial infarction and stroke in a population-based study...

..CONCLUSIONS: Aortic pulse wave velocity is an independent predictor of coronary heart disease and stroke in apparently healthy subjects...

..Large artery stiffening has adverse effects on cardiac structure and function and, therefore, may be associated with elevated circulating levels of amino-terminal pro-B-type natriuretic peptide (NT-proBNP)...

..We examined the SNPs in relation to the risk of CHD and MI in a large population based study of elderly population...

..We examined whether these glucocorticoid receptor gene polymorphisms are associated with growth in fetal and early postnatal life...

..We assessed the relation between the ACE I/D polymorphism and the risk of incident heart failure in normotensive and hypertensive subjects...

..Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children...

..For phenprocoumon dosage, the genes encoding CYP3A4 and ApoE might play a role...

..CONCLUSION: Atrophy of the hippocampus and amygdala on MRI in cognitively intact elderly people predicts dementia during a 6-year follow-up...

..We examined whether the PPARgamma2 Ala12 allele influences growth in early life and whether this association is modified by breast-feeding...

..The aim of this study is to examine whether cardiac size and function track in early childhood and are associated with fetal and early postnatal growth and blood flow characteristics...

..An example is catechol-O-methyltransferase (COMT), an estrogen-degrading enzyme involved in inactivation of catechol-estrogens. Its gene contains a functional valine to methionine substitution at codon 158...

..To examine whether infant growth rates are influenced by fetal growth characteristics and are associated with the risks of overweight and obesity in early childhood...

..This study was undertaken to investigate whether genetic variations in the estrogen receptor alpha (ESR1) gene are associated with incident AMD...

..A glucocorticoid receptor gene variant (ER22/23EK) is related to relative glucocorticoid resistance. We investigated whether the ER22/23EK allele is associated with dementia and structural brain abnormalities...

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..The aim of the present follow-up study was to investigate whether the enzyme activity of the human cytochrome P450 (CYP) 2C9 isoenzyme is associated with myocardial infarction...

..Furthermore, they generally did not examine explanatory mechanisms underlying the association between SES and temperament. We investigated the association between SES and temperament in infancy...

..The objective of this study was to examine whether this variant of the IGF-I gene is associated with blood pressure and left heart dimensions in early childhood...

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..We hypothesized that polymorphisms in host inflammatory response genes and genetic variation in S. aureus contribute to susceptibility to S. aureus carriage and infection...

..Variations in the deiodinase type 1 (DIO1) and type 2 (DIO2) genes that potentially alter thyroid hormone bioactivity may help in elucidating the role of thyroid function in AD...

..CONCLUSIONS: Elderly people with silent brain infarcts and white matter lesions are at a strongly increased risk of stroke, which could not be explained by the major stroke risk factors...

..Carriers of HFE C282Y and H63D mutations have elevated serum iron levels and may have an increased risk for stroke. We studied the association between HFE gene mutations, carotid atherosclerosis, and stroke...

..Commercial internet-based companies offer genome-wide scans to predict the risk of common diseases and personalize nutrition and lifestyle recommendations. These risk estimates are updated with every new gene discovery...

..Adverse environmental exposures lead to developmental adaptations in fetal life. The influences of maternal physical characteristics and lifestyle habits on first-trimester fetal adaptations and the postnatal consequences are not known...

..We investigated the association between APOE genotypes and left ventricular dysfunction in a population of community-dwelling elderly subjects...

..Our findings suggest that this promoter polymorphism or another functional polymorphism in linkage disequilibrium may be a genetic determinant of BMD levels and rate of bone loss in postmenopausal women...

..Evidence suggests that genetic variations in the estrogen receptor alpha (ESR1) gene may influence IHD risk, but the role of common sequence variations in the ESR1 gene is unclear...

..Taken together, our data suggest that the high levels of the antioxidant bilirubin may counteract the adverse effect of oxidative stress induced by iron overload. This may explain in part the reduced penetrance of the HFE mutations...

..These associations did not differ between strata of APOEepsilon4 genotype. Our observations do not suggest that variation in the MMP3 gene is causally involved in dementia or AD...

..52 (0.29-0.93) and 0.45 (0.23-0.86), for heterozygotes and H131 homozygotes, respectively; P trend=0.02). This is the first study showing that the H131 allele of FcgammaRIIa protects against advanced peripheral atherosclerosis...

..Furthermore, the BclI glucocorticoid receptor polymorphism did not predict the incidence of smoking cessation in the general elderly population...

..These results emphasize the need for prevention of progression of extracoronary atherosclerotic disease in men and women alike...

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..Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population...

..Greater fish and omega-3 (n-3) polyunsaturated fatty acid (PUFA) intake may reduce dementia risk; however, previous studies have reported conflicting results, which were largely based on short-term follow-up...

..Further studies are needed to identify the underlying causal mechanisms and the long-term consequences...

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..To investigate the relationship between the apolipoprotein E (APOE) gene and the risk of mortality in normal weight, overweight and obese individuals...

..The results suggest that coronary calcification as detected by electron-beam CT may be useful to identify subjects at high risk of stroke...

..25 [2.1-71], P = 0.003). A locus on chromosome 18p in patients with high BMI was suggested earlier by Parker et al. Our study is the first to confirm this locus...