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Biomedical subjects

Albert Hofman

Publications and source records attributed to Albert Hofman.

At least 181 records · Page 10Linked to original sources
PubMed2003

Repeated nitrate prescriptions as a potential marker for angina pectoris. A comparison with medical information from the Rotterdam Study.

OBJECTIVE: The objective of this study was to determine whether pharmacy records of nitrate prescriptions could be used as a marker of angina pectoris. METHOD: This study was conducted within the Rotterdam Study, a prospective follow-up study which started in 1991 and included 7983 elderly subjects. During follow-up, 1601 subjects filled a first prescription for a nitrate and later filled at least one other prescription for nitrates according to pharmacy records. After excluding subjects who started using nitrates in 1991 and who had less than one year of medication history, we took a random sample of 78 subjects (10%). We studied discharge and outpatient cardiologist letters and files from general practitioners for additional information on angina pectoris in these subjects, and allocated patients to one of three categories according to the possibility of the initial diagnosis of angina being correct. RESULTS: From the random sample of 78, additional information was available on 75 subjects. Definite angina pectoris was present in 33, probable angina pectoris in 18, and possible angina pectoris in 19 subjects. Five subjects had no angina pectoris. Therefore, 93% had at least a possible diagnosis while 68% had at least a probable diagnosis of angina pectoris. The positive predictive value of 2 nitrate prescriptions of which at least one was for rescue therapy was 94%. CONCLUSIONS: We conclude that the use of more than one nitrate prescription can be used as a marker for angina pectoris. This marker may be useful in epidemiological studies.

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PubMed2003

Epidemiology of age-related maculopathy: a review.

Age-related maculopathy (ARM) is a degenerative disease of the retina and the leading cause of incurable blindness and visual impairment in industrialized countries. By definition, ARM is confined to the age-category above 50 years. The aetiology of ARM is still unknown, despite intensive research on many fronts. In this paper, we provide a review of the epidemiology of ARM. The most prominent findings were an exponential increase in frequency with age, a significant familial and genetic component, and a strong association with smoking. Other risk factors that were found less consistently were atherosclerosis, low intake of antioxidant nutrients, and cataract extraction. Future studies, both observational and experimental, will hopefully identify more risk factors that are amenable to prevention.

Age of Onset↗
PubMed2003

A population-based study of the effect of the HFE C282Y and H63D mutations on iron metabolism.

The C282Y and H63D mutations in the HFE gene are important causes of hemochromatosis. In the elderly, these mutations might be associated with increased morbidity because of the lifelong accumulation of iron. In a population-based sample of the elderly, we determined the value of genotyping for HFE mutations to screen for subclinical hemochromatosis. HFE genotype frequencies were determined in a random group of 2095 subjects (55 years and over). In this random group, we selected within the six genotype groups a total of 342 individuals and measured their serum transferrin saturation, iron and ferritin levels. We also estimated the heritability and parameters needed to evaluate screening, including the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of HFE genotypes. Iron parameters were significantly increased in subjects homozygous, heterozygous or compound heterozygous. The effect of the mutations was more pronounced in men than in women. For the H63D mutation, an allele dose effect was observed. The HFE gene explained about 5% of the variability in serum iron indices. The PPV for hemochromatosis for the C282Y homozygous was 100% in men and 67% in women. The NPV of the wild-type allele was 97% for both men and women. The sensitivity of both mutations was 70% for men and 52% for women and the specificity was 62% for men and 64% for women. Our study shows that the HFE C282Y and H63D are determinants of iron parameters in the elderly and will be effective in detecting individuals at high risk of hemochromatosis. However, when screening based on these two mutations, some individuals with subclinical hemochromatosis will be missed.

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PubMed2003

Late-life depression is associated with arterial stiffness: a population-based study.

OBJECTIVES: To determine whether arterial stiffness is associated with depression in the elderly. DESIGN: Population-based cross-sectional study. SETTING: In Ommoord, a suburb of Rotterdam, the Netherlands. PARTICIPANTS: Three thousand seven hundred four subjects of the Rotterdam Study aged 60 and older. MEASUREMENTS: Arterial stiffness was assessed using the distensibility of the carotid artery and the carotid-femoral pulse wave velocity. All participants were screened for depressive symptoms with the Center for Epidemiologic Studies-Depression scale. Those with depressive symptoms had a psychiatric evaluation to establish a diagnosis of depressive disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. RESULTS: Participants with increased arterial stiffness were more likely to have depressive symptoms. Odds ratios (ORs) for depressive symptoms were 1.24 (95% confidence interval (CI) = 1.01-1.52) per standard deviation decrease in carotid distensibility and 1.17 (95% CI = 1.00-1.38) per standard deviation increase in aortic pulse wave velocity. The association was stronger for depressive disorders meeting DSM-IV criteria (OR = 1.44, 95% CI = 1.03-2.03; OR = 1.48, 95% CI = 1.16-1.90, respectively). Control for atherosclerosis, as measured by the ankle-to-brachial index or presence of plaques in the carotid artery, did not change the associations. CONCLUSION: This study shows an association between arterial stiffness and depression in the elderly. The findings are compatible with the vascular depression hypothesis. These data suggest that arterial stiffness may partly cause the proposed relationship between vascular factors and depression.

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PubMed2003

Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study.

BACKGROUND: It has been hypothesized that n-3 polyunsaturated fatty acids (PUFAs) are involved in mood regulation, but epidemiologic evidence for such a link in the general population is lacking. OBJECTIVE: This study examined whether community-dwelling elderly persons with depression have a fatty acid composition that is different from that of nondepressed persons. DESIGN: We screened 3884 adults aged > or = 60 y for depressive symptoms as part of the Rotterdam Study. Subjects who screened positive had a psychiatric interview to diagnose depressive disorders. All eligible subjects had their blood drawn for measurement of plasma phospholipid concentrations. We compared percentages of n-3 and n-6 PUFAs and their ratios between 264 subjects with depressive symptoms, including 106 subjects with depressive disorders, and 461 randomly selected reference subjects. We also investigated whether atherosclerosis or the inflammatory response as measured by C-reactive protein underlies the relation between fatty acid composition and depression. RESULTS: Subjects with depressive disorders had a higher ratio of n-6 to n-3 PUFAs, but differences in individual PUFAs were mostly small. However, depressed subjects with normal CRP concentrations (< 1.5 mg/L) had a substantially altered fatty acid composition; percentages of n-3 PUFAs and ratios of n-6 to n-3 PUFAs were significantly lower and higher, respectively, in subjects with depressive disorders than in control subjects [5.2% compared with 5.9% (P = 0.02) and 7.2 compared with 6.6 (P = 0.01), respectively]. This relation was not due to atherosclerosis. CONCLUSIONS: In community-dwelling persons, fatty acid composition is related to depression. Because this relation was not secondary to inflammation, atherosclerosis, or possible confounders, it suggests a direct effect of fatty acid composition on mood.

Cohort Studies↗
PubMed2003

Inflammatory proteins and depression in the elderly.

BACKGROUND: Clinical studies suggest that depression may be accompanied by an activation of the inflammatory response system. We investigated the relation of cytokine interleukin-6 and the acute phase proteins alpha1-antichymotrypsin and C-reactive protein with depression in a population-based study. METHODS: We screened for depressive symptoms 3884 adults at age 60 and older living in a district of Rotterdam, and performed a psychiatric work-up on those who were screened positive. All subjects had blood drawn. We compared levels of inflammation markers adjusted for smoking, stroke, functional disability and cognitive score for 263 cases with depressive symptoms (including 106 subjects with depressive disorders) and 461 randomly selected reference subjects. RESULTS: Age- and gender-adjusted analyses suggested associations of alpha1-antichymotrypsin and C-reactive protein with depressive disorders, but these associations disappeared after adjustment for additional confounding factors. Even after adjustment, increased levels of interleukin-6 were related to depressive disorders (odds ratio per standard deviation increase in interleukin-6 = 1.47; 95% confidence interval = 1.15-1.89). Further analyses demonstrated that this relation was mainly attributable to the subjects with high interleukin-6 concentrations, suggesting a threshold effect. CONCLUSIONS: Interleukin-6 levels were strongly increased in some subjects with depressive disorders, possibly indicating a specific immunologic process. However, the associations of acute phase proteins with depression in this population-based study could be explained by confounding.

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PubMed2003

The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial.

BACKGROUND: The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago, but are less clear in those with mildly to moderately elevated blood pressure. OBJECTIVE: To assess whether candesartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events, cognitive decline and dementia. DESIGN: Prospective, double-blind, randomized, parallel-group study conducted in 1997-2002. SETTING AND PARTICIPANTS: The study was of 4964 patients aged 70-89 years, with systolic blood pressure 160-179 mmHg, and/or diastolic blood pressure 90-99 mmHg, and a Mini Mental State Examination (MMSE) test score >or= 24. A total of 527 centres in 15 countries participated in the study. INTERVENTION: Patients were assigned randomly to receive the angiotensin receptor blocker candesartan or placebo, with open-label active antihypertensive therapy added as needed. As a consequence, active antihypertensive therapy was extensively used in the control group (84% of patients). Mean follow-up was 3.7 years. MAIN OUTCOME MEASURES: The primary outcome measure was major cardiovascular events, a composite of cardiovascular death, non-fatal stroke and non-fatal myocardial infarction. Secondary outcome measures included cardiovascular death, non-fatal and fatal stroke and myocardial infarction, cognitive function measured by the MMSE and dementia. RESULTS: Blood pressure fell by 21.7/10.8 mmHg in the candesartan group and by 18.5/9.2 mmHg in the control group. A first major cardiovascular event occurred in 242 candesartan patients and in 268 control patients; risk reduction with candesartan was 10.9% [95% confidence interval (CI), -6.0 to 25.1, P = 0.19]. Candesartan-based treatment reduced non-fatal stroke by 27.8% (95% CI, 1.3 to 47.2, P = 0.04), and all stroke by 23.6% (95% CI, -0.7 to 42.1, P = 0.056). There were no significant differences in myocardial infarction and cardiovascular mortality. Mean MMSE score fell from 28.5 to 28.0 in the candesartan group and from 28.5 to 27.9 in the control group (P = 0.20). The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups. CONCLUSIONS: In elderly hypertensive patients, a slightly more effective blood pressure reduction during candesartan-based therapy, compared with control therapy, was associated with a modest, statistically non-significant, reduction in major cardiovascular events and with a marked reduction in non-fatal stroke. Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions. Both treatment regimens were generally well tolerated.

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PubMed2003

Adherence to and dosing of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors in the general population differs according to apolipoprotein E-genotypes.

Discontinuation and poor adherence to therapy are major problems during long-term treatment, particularly with cholesterol lowering drugs. Several studies have indicated that the cholesterol lowering effect of statins differs according to apolipoprotein (apo)E genotypes. Low-density lipoprotein-cholesterol lowering capacity appears to be smaller in subjects with the epsilon(4) allele. To assess whether the use of statins in daily practice differs according to apoE genotypes, we used data from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, which started in 1990 and included 7983 subjects aged 55 years or more. During follow-up, there were 798 subjects who started to use statins. We used a Cox proportional hazard model to determine the rate of discontinuation in the first 3 years of statin use. Subjects on statin therapy with epsilon(2)epsilon(2) and epsilon(4)epsilon(4) genotypes showed a trend towards higher dosages than subjects with the other genotypes. Relative to subjects with the epsilon(2)epsilon(3) genotype, those with the epsilon(4)epsilon(4) genotype had a risk of 2.28 [95% confidence interval (CI) 1.02-5.12] to discontinue statins within 3 years. In women, this relative risk was 1.70 (CI 0.53-5.42) versus 3.18 (CI 1.01-10.03) in men. The apoE genotype is associated with discontinuation of statins. This suggests that subjects who are genetically prone to develop hypercholesterolemia show the highest risk of discontinuation of treatment.

Apolipoproteins E↗
PubMed2003

Atrial fibrillation and the prothrombotic state in the elderly: the Rotterdam Study.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is a major cause of stroke among the elderly. Evidence for a prothrombotic state in AF is controversial, and there is a lack of studies among the elderly. We studied the relationships between AF and 3 prothrombotic plasma markers-von Willebrand factor (vWf; a marker of endothelial damage/dysfunction), soluble P-selectin (sP-sel; a marker of platelet activation), and fibrinogen-in a matched case-control study nested within a large community-based study of an elderly population. METHODS: We identified 162 elderly participants (mean+/-SD age, 78+/-8 years; 51% male) in the Rotterdam Study with documented AF and matched each case by age and sex to 2 population controls. vWf and sP-sel were measured by enzyme-linked immunosorbent assay; fibrinogen was measured with the Clauss method. We used conditional logistic regression analysis to assess the relationships between the markers and AF, adjusting for potential confounders. RESULTS: There were no significant relationships between either fibrinogen (P=0.8) or sP-sel (P=0.6) and AF. However, a positive linear relationship between vWf level and presence of AF remained significant after adjustment for potential confounders among women (odds ratio [OR], 1.17; 95% CI, 1.02 to 1.34) per 10-IU/dL increase in vWf but not among men (OR, 1.06; 95% CI, 0.96 to 1.17). CONCLUSIONS: We observed a positive relationship between AF and plasma vWf (or endothelial damage/dysfunction) in our elderly population, which was most apparent among women. Fibrinogen and sP-sel levels were unrelated to AF. The prothrombotic state of AF may be subject to sex differences, but longitudinal studies are needed to determine the relationship between these plasma markers and stroke risk.

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PubMed2003

Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study.

BACKGROUND AND PURPOSE: The prevalence of silent brain infarcts in healthy elderly people is high, and these lesions are associated with an increased risk of stroke. The incidence of silent brain infarcts is unknown. We investigated the incidence and cardiovascular risk factors for silent brain infarcts. METHODS: The Rotterdam Scan Study is a prospective, population-based cohort study of 1077 participants 60 to 90 years of age. All participants underwent cranial MRI in 1995 to 1996, and 668 participants had a second MRI in 1999 to 2000 (response rate, 70%) with a mean interval of 3.4 years. We assessed cardiovascular risk factors by interview and physical examination at baseline. Associations between risk factors and incident silent infarcts were analyzed by multiple logistic regression. RESULTS: Ninety-three participants (14%) had > or =1 new infarcts on the second MRI; of these, 81 had only silent and 12 had symptomatic infarcts. The incidence of silent brain infarcts strongly increased with age and was 5 times higher than that of symptomatic stroke. A prevalent silent brain infarct strongly predicted a new silent infarct on the second MRI (age- and sex-adjusted odds ratio, 2.9; 95% confidence interval, 1.7 to 5.0). Age, blood pressure, diabetes mellitus, cholesterol and homocysteine levels, intima-media thickness, carotid plaques, and smoking were associated with new silent brain infarcts in participants without prevalent infarcts. CONCLUSIONS: The incidence of silent brain infarcts on MRI in the general elderly population strongly increases with age. The cardiovascular risk factors for silent brain infarcts are similar to those for stroke.

Age Distribution↗
PubMed2003

Relationship between refraction and prevalent as well as incident age-related maculopathy: the Rotterdam Study.

PURPOSE: To study the relationship between baseline spherical equivalents (SphE) of refraction and prevalent as well as incident age-related maculopathy (pARM and iARM, respectively). METHODS: The study was performed as part of the Rotterdam Study, a population-based, prospective cohort study. The SphE (in diopters), measured with autorefraction and subjective optimization, was recorded in 6209 subjects aged 55 years or more. Aphakic or pseudophakic eyes at baseline were excluded. Stereoscopic transparencies of the macular region were graded according to the International Classification and Grading System. ARM was defined as large soft drusen with pigmentary changes, or indistinct drusen, or atrophic or neovascular age-related macular degeneration (AMD). For the prevalence analyses, ARM was classified into no, p(early)ARM, or pAMD, and in each subject the eye with the most advanced ARM and the corresponding refraction was selected. After a mean 5.2 years of follow-up, 4935 subjects had complete data for these incidence analyses. In each subject, the eye with iARM was selected. RESULTS: The age- and gender-adjusted odds ratio (OR) of pARM (n = 536) for every diopter of progress toward hyperopia was 1.09 (95% confidence interval [CI]1.04-1.13). For p(early)ARM (n = 440) the OR was 1.09 (1.04-1.14) and for pAMD (n = 96) the OR was 1.09 (1.00-1.19). Baseline refraction was significantly associated with increased risk of iARM (n = 497). For each diopter of progress toward hyperopia the OR was 1.05 (95% CI 1.01-1.10). Additional adjustments for smoking, atherosclerosis, and blood pressure did not alter the relationship. CONCLUSIONS: These population-based incidence data confirm results from prevalence and case-control studies that there is an association between hyperopia and ARM.

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PubMed2003

Blood pressure, atherosclerosis, and the incidence of age-related maculopathy: the Rotterdam Study.

PURPOSE: To determine whether blood pressure and subclinical atherosclerosis are associated with incident age-related maculopathy (ARM). METHODS: The study was performed within the Rotterdam Study, a population-based, prospective cohort study in Rotterdam, The Netherlands. A total of 4822 subjects who at baseline were aged 55 years more, were free of ARM, and participated in at least one of two follow-up examinations after a mean of 2 and 6.5 years, were included in the study. At baseline, blood pressure and the presence of atherosclerosis were determined. ARM was assessed according to the International Classification and Grading System and defined as large, soft drusen with pigmentary changes; indistinct drusen; or atrophic or neovascular age-related macular degeneration. RESULTS: After a mean follow-up of 5.2 years, incident ARM was diagnosed in 417 subjects. Increased systolic blood pressure or pulse pressure was associated with a higher risk of ARM. Adjusted for age, gender, smoking, total and high-density lipoprotein cholesterol, body mass index, and diabetes mellitus, odds ratios (OR) per 10-mm Hg increase were 1.08 (95% confidence interval [CI]: 1.03-1.14) and 1.11 (95% CI: 1.04-1.18), respectively. Moreover, different measures of atherosclerosis were associated with the risk of ARM. An increase in carotid wall thickness (OR per 1 SD, 1.15; 95% CI: 1.03-1.28) increased the risk of ARM. The lowest compared with the highest tertile of ankle-arm index had an OR of 1.32 (95% CI: 1.00-1.75). A weak association was found between aortic calcifications and the risk of ARM. CONCLUSIONS: Elevated systolic blood or pulse pressure or the presence of atherosclerosis may increase the risk of development of ARM.

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PubMed2003

Association between an insulin-like growth factor I gene promoter polymorphism and bone mineral density in the elderly: the Rotterdam Study.

Studies of the roles of variants of the IGF-I gene in the regulation of bone mineral density (BMD) have yielded conflicting results. We examined the role of a microsatellite repeat polymorphism in one of the promoter regions of the IGF-I gene in relation to femoral BMD in elderly women and men from the Rotterdam Study. We studied 5648 and 4134 individuals at baseline and follow-up ( approximately 2 yr later), respectively. Femoral BMD measurements were performed using dual energy x-ray absorptiometry. In women, baseline BMD levels were, on the average, 0.02 g/cm(2) [95% confidence interval (CI) for difference, -0.03, -0.00 g/cm(2)] lower in individuals without the 192-bp allele as compared with the homozygotes for the allele (P = 0.03). The mean rate of BMD change from baseline to follow-up was -6.9 mg/cm(2) (95% CI, -10.8, -3.0), -4.5 mg/cm(2) (95% CI, -6.4, -2.5), and -2.3 mg/cm(2) (95% CI, -4.2, 0.3) in noncarriers, heterozygotes, and homozygotes for the 192-bp allele, respectively (P trend = 0.03). Adjustment for age and body mass index did not essentially change this relation. No such effects were observed in men. 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.

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PubMed2003

Cdx-2 polymorphism in the promoter region of the human vitamin D receptor gene determines susceptibility to fracture in the elderly.

UNLABELLED: A Cdx-2 binding site polymorphism (G to A) in the promoter region of the human vitamin D receptor gene was reported. In an ecological study in eight ethnic groups and an association study in 2848 elderly whites, we found the A-allele to be associated with decreased fracture risk. Our findings expand previous similar findings in a Japanese study to whites and show a relationship with fracture risk of this functional polymorphism. INTRODUCTION: A single nucleotide polymorphism (SNP) within a binding site of the intestinal-specific transcription factor Cdx-2 in the promoter region of the human vitamin D receptor (VDR) gene was previously reported. It was found to modulate the transcription of the hVDR gene and to be associated with decreased bone mineral density in a small group of postmenopausal Japanese women. In this study, we investigated the relationship between the VDR Cdx-2 genotype and risk of fracture. METHODS: We first determined the location of this SNP in the VDR gene by sequencing analysis, and we developed an allele-specific multiplex polymerase chain reaction test to determine the Cdx-2 genotype. We then performed an ecological study in eight ethnic groups and an association analysis in a large epidemiological cohort of 2848 Dutch white men and women, > or = 55 years old. RESULTS AND CONCLUSIONS: The location of the G to A substitution was found in the promoter region of exon le (le-G-1739A) of the VDR gene. By comparing the frequency of the A-allele in eight different ethnic groups, we observed a negative correlation between prevalence of the A-allele and published hip fracture incidence rates in these ethnic groups (p = 0.006 for men and p = 0.02 for women), suggesting a protective effect of this allele on fracture risk. Subsequently, in the association study, the A-allele (population frequency 19%) was observed to have a protective effect on occurrence of osteoporotic fractures, especially for nonvertebral fracture in women (relative risk of AA versus GG genotype is 0.2; 95% CI, 0.05-0.8). This effect remained after adjustment for age, weight, and bone mineral density. We conclude that the A-allele of the VDR Cdx-2 polymorphism is present in whites, albeit at low frequency, and show a protective effect of this allele on risk of fracture.

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PubMed2003

A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels.

OBJECTIVE: Recent studies have demonstrated an association between a 192 bp polymorphism of the IGF-I gene and total IGF-I serum levels, birth weight, body height and the risk of developing diabetes and cardiovascular diseases later on in life. This IGF-I gene polymorphism in the promoter region of the IGF-I gene may directly influence the expression of IGF-I. In the present study we evaluated the role of this polymorphism in the age-related decline in serum IGF-I levels. SUBJECTS AND METHODS: All subjects were participants of the Rotterdam Study, a population-based cohort study of diseases in the elderly. We studied a total group of 346 subjects, who comprised two subgroups: a randomly selected population-based sample of 196 subjects, and a group of 150 subjects selected on IGF-I genotype. In the total group of 346 individuals the relationship between this 192 bp polymorphism and the age-related decline in circulating total IGF-I levels was studied. RESULTS: Homozygous carriers of the 192 bp allele demonstrated significant decline in serum IGF-I with age (r=-0.29, P=0.002). This decline is similar to that seen in the general population. An age-related decline in serum total IGF-I was not observed in heterozygotes (r=-0.06, P=0.48) and non-carriers (r = -0.12, P=0.32). Interestingly, the relationship between age and serum IGF-binding protein-3 levels showed the same pattern. CONCLUSION: We observed only in homozygous carriers of the 192 bp alleles of the IGF-I gene an age-related decline in circulating total IGF-I levels, but not in heterozygotes and non-carriers of the 192 bp allele. We hypothesize that this IGF-I gene polymorphism directly or indirectly influences GH-mediated regulation of IGF-I secretion.

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PubMed2003

A genome-wide search for genes involved in type 2 diabetes in a recently genetically isolated population from the Netherlands.

Multiple genes, interacting with the environment, contribute to the susceptibility to type 2 diabetes. We performed a genome-wide search to localize type 2 diabetes susceptibility genes in a recently genetically isolated population in the Netherlands. We identified 79 nuclear families with type 2 diabetes who were related within 13 generations and performed a 770-marker genome-wide scan search for shared founder alleles. Twenty-six markers yielded a logarithm of odds (LOD) score >0.59 (nominal P < 0.05), of which 7 reached LOD scores >1.17 (nominal P < 0.01). The strongest evidence for a type 2 diabetes locus was at marker D18S63 on chromosome 18p (LOD 2.3, P = 0.0006). This region was investigated further using additional markers. For one of these markers (D18S1105), we found a significant association with type 2 diabetes (odds ratio 6.7 [95% CI 1.5-30.7], P = 0.005 for the 97-bp allele, assuming a dominant model), which increased when limiting the analysis to patients with high BMI (12.25 [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.

Alleles↗
PubMed2002

Dietary intake of antioxidants and risk of Alzheimer disease.

CONTEXT: Laboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease. Therefore, the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress. OBJECTIVE: To determine whether dietary intake of antioxidants is related to risk of Alzheimer disease. DESIGN AND SETTING: The Rotterdam Study, a population-based, prospective cohort study conducted in the Netherlands. PARTICIPANTS: A total of 5395 participants who, at baseline (1990-1993), were aged at least 55 years, free of dementia, and noninstitutionalized and had reliable dietary assessment. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for incident dementia. MAIN OUTCOME MEASURES: Incidence of Alzheimer disease, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) criteria, associated with dietary intake of beta carotene, flavonoids, vitamin C, and vitamin E. RESULTS: After a mean follow-up of 6 years, 197 participants developed dementia, of whom 146 had Alzheimer disease. When adjustments were made for age, sex, baseline Mini-Mental State Examination score, alcohol intake, education, smoking habits, pack-years of smoking, body mass index, total energy intake, presence of carotid plaques, and use of antioxidative supplements, high intake of vitamin C and vitamin E was associated with lower risk of Alzheimer disease (rate ratios [RRs] per 1-SD increase in intake were 0.82 [95% confidence interval [CI], 0.68-0.99] and 0.82 [95% CI, 0.66-1.00], respectively). Among current smokers, this relationship was most pronounced (RRs, 0.65 [95% CI, 0.37-1.14] and 0.58 [95% CI, 0.30-1.12], respectively) and also was present for intake of beta carotene (RR, 0.49 [95% CI, 0.27-0.92]) and flavonoids (RR, 0.54 [95% CI, 0.31-0.96]). The associations did not vary by education or apolipoprotein E genotype. CONCLUSION: High dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease.

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