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1.
Mol Psychiatry ; 17(11): 1116-29, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21876539

RESUMEN

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).


Asunto(s)
Moléculas de Adhesión Celular/genética , Café/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A2/genética , Ingestión de Líquidos/genética , Estudio de Asociación del Genoma Completo/métodos , Antígenos de Neoplasias/genética , Proteínas Reguladoras de la Apoptosis/genética , Cafeína/farmacología , Línea Celular , Femenino , Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Proteínas Serina-Treonina Quinasas/genética , Población Blanca/genética
2.
Neurology ; 67(2): 315-8, 2006 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-16864826

RESUMEN

BACKGROUND: Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson disease (PD), through neurotoxic effects. Higher dietary intakes of folate, vitamin B12, and vitamin B6 (cofactors in homocysteine metabolism) might decrease the risk of PD through decreasing plasma homocysteine. Moreover, vitamin B6 might influence the risk of PD through antioxidant effects unrelated to homocysteine metabolism and through its role in dopamine synthesis. METHODS: In the Rotterdam Study, a prospective, population-based cohort study of people aged 55 years and older, the authors evaluated the association between dietary intake of folate, vitamin B12, and vitamin B6 and the risk of incident PD among 5,289 participants who were free of dementia and parkinsonism and underwent complete dietary assessment at baseline. PD was assessed through repeated in-person examination and continuous monitoring by computer linkage to medical records. Data were analyzed using Cox proportional hazards regression analysis. RESULTS: After a mean follow-up of 9.7 years, the authors identified 72 participants with incident PD. Higher dietary intake of vitamin B6 was associated with a significantly decreased risk of PD (hazard ratio per SD, 0.69 [95% CI 0.50 to 0.96]; for highest vs lowest tertile, 0.46 [0.22 to 0.96]). Stratified analyses showed that this association was restricted to smokers. No association was observed for dietary folate and vitamin B(12). CONCLUSIONS: Dietary vitamin B6 may decrease the risk of Parkinson disease, probably through mechanisms unrelated to homocysteine metabolism.


Asunto(s)
Dietoterapia/estadística & datos numéricos , Ácido Fólico/administración & dosificación , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/prevención & control , Medición de Riesgo/métodos , Vitamina B 12/administración & dosificación , Vitamina B 6/administración & dosificación , Administración Oral , Estudios de Cohortes , Suplementos Dietéticos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Factores de Riesgo , Resultado del Tratamiento
3.
Neurology ; 64(12): 2040-5, 2005 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-15985568

RESUMEN

BACKGROUND: Unsaturated fatty acids are important constituents of neuronal cell membranes and have neuroprotective, antioxidant, and anti-inflammatory properties. OBJECTIVE: To determine if a high intake of unsaturated fatty acids might be associated with a lower risk of Parkinson disease (PD). METHODS: In the Rotterdam Study, a prospective population-based cohort study of people ages > or =55, the association between intake of unsaturated fatty acids and the risk of incident PD was evaluated among 5,289 subjects who were free of dementia and parkinsonism and underwent complete dietary assessment at baseline. PD was assessed through repeated in-person examination, and the cohort was continuously monitored by computer linkage to medical records. The data were analyzed using Cox proportional hazards regression models. RESULTS: After a mean follow-up of 6.0 years, 51 participants with incident PD were identified. Intakes of total fat, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were significantly associated with a lower risk of PD, with an adjusted hazard ratio per SD increase of energy-adjusted intake of 0.69 (95% CI 0.52 to 0.91) for total fat, of 0.68 (95% CI 0.50 to 0.94) for MUFAs, and 0.66 (95% CI 0.46 to 0.96) for PUFAs. No associations were found for dietary saturated fat, cholesterol, or trans-fat. CONCLUSION: These findings suggest that high intake of unsaturated fatty acids might protect against Parkinson disease.


Asunto(s)
Encéfalo/metabolismo , Encéfalo/fisiopatología , Grasas Insaturadas en la Dieta/uso terapéutico , Ácidos Grasos Insaturados/uso terapéutico , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/prevención & control , Anciano , Estudios de Cohortes , Grasas Insaturadas en la Dieta/metabolismo , Ingestión de Energía/fisiología , Ácidos Grasos Monoinsaturados/metabolismo , Ácidos Grasos Monoinsaturados/uso terapéutico , Ácidos Grasos Insaturados/metabolismo , Conducta Alimentaria/fisiología , Femenino , Estudios de Seguimiento , Alimentos Formulados/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Enfermedad de Parkinson/metabolismo , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios
4.
Neurology ; 59(12): 1915-21, 2002 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-12499483

RESUMEN

OBJECTIVE: To examine whether high intake of total fat, saturated fatty acids (saturated fat), trans fatty acids (trans fat), and cholesterol and low intake of monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n-6 PUFA, and n-3 PUFA are associated with increased risk of dementia and its subtypes. METHOD: Data from the Rotterdam Study, a prospective cohort study among elderly, were used. At baseline (1990 to 1993), 5,395 subjects had normal cognition, were noninstitutionalized, and underwent complete dietary assessment by a semiquantitative food-frequency questionnaire. The cohort was continuously monitored for incident dementia, and re-examinations were performed in 1993 to 1994 and 1997 to 1999. The association between fat intake and incident dementia was examined by Cox's proportional hazards models. RESULTS: After a mean follow-up of 6.0 years, 197 subjects developed dementia (146 AD, 29 vascular dementia). High intake of total, saturated, trans fat, and cholesterol and low intake of MUFA, PUFA, n-6 PUFA, and n-3 PUFA were not associated with increased risk of dementia or its subtypes. Rate ratios of dementia per standard deviation increase in intake were for total fat 0.93 (95% CI 0.81 to 1.07), for saturated fat 0.91 (95% CI 0.79 to 1.05), for trans fat 0.90 (95% CI 0.77 to 1.06), for cholesterol 0.93 (95% CI 0.80 to 1.08), for MUFA 0.96 (95% CI 0.84 to 1.10), for PUFA 1.05 (95% CI 0.80 to 1.38), for n-6 PUFA 1.03 (95% CI 0.77 to 1.36), and for n-3 PUFA 1.07 (95% CI 0.94 to 1.22). CONCLUSION: High intake of total, saturated, and trans fat and cholesterol and low intake of MUFA, PUFA, n-6 PUFA, and n-3 PUFA were not associated with increased risk of dementia or its subtypes.


Asunto(s)
Demencia/epidemiología , Dieta , Grasas de la Dieta/efectos adversos , Factores de Edad , Anciano , Antioxidantes/uso terapéutico , Colesterol en la Dieta/efectos adversos , Estudios de Cohortes , Demencia/diagnóstico , Educación , Metabolismo Energético/fisiología , Ácidos Grasos/efectos adversos , Ácidos Grasos Monoinsaturados , Ácidos Grasos Omega-3 , Ácidos Grasos Omega-6 , Ácidos Grasos Insaturados , Femenino , Estudios de Seguimiento , Humanos , Masculino , Países Bajos/epidemiología , Pruebas Neuropsicológicas , Medición de Riesgo , Factores Sexuales , Vitamina E/uso terapéutico
6.
Arch Intern Med ; 159(18): 2170-4, 1999 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-10527294

RESUMEN

BACKGROUND: Epidemiological studies have indicated a protective role of dietary flavonoids in cardiovascular disease, but evidence is still conflicting. Tea is the major dietary source for flavonoids in Western populations. We studied the association of tea intake with aortic atherosclerosis in a general population. METHODS: The present analysis formed part of the Rotterdam Study, a prospective study of men and women 55 years and older. Dietary intakes were assessed at baseline by a trained dietician who used a semiquantitative food frequency questionnaire. Calcified plaques in the abdominal aorta were radiographically detected after 2 to 3 years of follow-up. Aortic atherosclerosis was classified as "mild," "moderate," or "severe," according to the length of the calcified area (<1 cm, 1-5 cm, and >5 cm, respectively). The association of tea intake with severity of aortic atherosclerosis was studied in 3454 subjects who were free of cardiovascular disease at baseline. Data were analyzed by logistic regression, adjusting for age, sex, body mass index (calculated as weight in kilograms divided by the square of height in meters), smoking, education, and intake of alcohol, coffee, vitamin antioxidants, total fat, and total energy. RESULTS: Multivariable analyses showed a significant, inverse association of tea intake with severe aortic atherosclerosis. Odds ratios decreased from 0.54 (95% confidence interval [CI], 0.32-0.92) for drinking 125 to 250 mL (1-2 cups) of tea to 0.31 (CI, 0.16-0.59) for drinking more than 500 mL/d (4 cups per day). The associations were stronger in women than in men. The association of tea intake with mild and moderate atherosclerosis was not statistically significant. CONCLUSION: This study indicates a protective effect of tea drinking against ischemic heart disease.


Asunto(s)
Arteriosclerosis/prevención & control , Flavonoides/farmacología , , Arteriosclerosis/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Países Bajos/epidemiología , Oportunidad Relativa , Estudios Prospectivos , Riesgo , Té/química
7.
Am J Clin Nutr ; 69(2): 261-6, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9989690

RESUMEN

BACKGROUND: Epidemiologic studies have shown dietary antioxidants to be inversely correlated with ischemic heart disease. OBJECTIVE: We investigated whether dietary beta-carotene, vitamin C, and vitamin E were related to the risk of myocardial infarction (MI) in an elderly population. DESIGN: The study sample consisted of 4802 participants of the Rotterdam Study aged 55-95 y who were free of MI at baseline and for whom dietary data assessed by a semiquantitative food frequency questionnaire were available. During a 4-y follow-up period, 124 subjects had an MI. The association between energy-adjusted beta-carotene, vitamin C, and vitamin E intakes and risk of MI was examined by multivariate logistic regression. RESULTS: Risk of MI for the highest compared with the lowest tertile of beta-carotene intake was 0.55 (95% CI: 0.34, 0.83; P for trend = 0.013), adjusted for age, sex, body mass index, pack-years, income, education, alcohol intake, energy-adjusted intakes of vitamin C and E, and use of antioxidative vitamin supplements. When beta-carotene intakes from supplements were considered, the inverse relation with risk of MI was slightly more pronounced. Stratification by smoking status indicated that the association was most evident in current and former smokers. No association with risk of MI was observed for dietary vitamin C and vitamin E. CONCLUSION: The results of this observational study in the elderly population of the Rotterdam Study support the hypothesis that high dietary beta-carotene intakes may protect against cardiovascular disease. We did not observe an association between vitamin C or vitamin E and MI.


Asunto(s)
Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Dieta , Infarto del Miocardio/prevención & control , Vitamina E/administración & dosificación , beta Caroteno/administración & dosificación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Fumar , Encuestas y Cuestionarios
8.
Am J Clin Nutr ; 60(1): 129-35, 1994 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8017327

RESUMEN

In a double-blind controlled trial, 91 middle-aged and elderly women with mild to moderate hypertension who were not on antihypertensive medication were randomly assigned to treatment with magnesium aspartate-HCl (20 mmol Mg/d) or placebo for 6 mo. Magnesium aspartate-HCl in the given dose was well-tolerated and was not associated with an increased frequency of diarrhea compared with placebo. At the end of the study, systolic blood pressure had fallen by 2.7 mm Hg (95% CI -1.2, 6.7; P = 0.18) and diastolic blood pressure by 3.4 mm Hg (1.3, 5.6; P = 0.003) more in the magnesium group than in the placebo group. Blood pressure response was not associated with baseline magnesium status, as measured by dietary magnesium intake and urinary magnesium excretion. Urinary magnesium excretion in the magnesium group increased by 50% during the intervention period. No changes were seen in other biochemical indexes, including serum concentrations of total and high-density-lipoprotein cholesterol. The findings suggest that oral supplementation with magnesium aspartate-HCl may lower blood pressure in subjects with mild to moderate hypertension.


Asunto(s)
Ácido Aspártico/uso terapéutico , Hipertensión/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Ácido Aspártico/administración & dosificación , Ácido Aspártico/efectos adversos , Presión Sanguínea/efectos de los fármacos , Peso Corporal , Diarrea/inducido químicamente , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Magnesio/sangre , Magnesio/orina , Persona de Mediana Edad , Cooperación del Paciente , Renina/sangre
9.
JAMA ; 261(8): 1161-4, 1989 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-2915438

RESUMEN

To study the association between selenium status and the risk of myocardial infarction, we compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls (31.3 +/- 8.4 U/g of hemoglobin and 28.0 +/- 8.1 U/g of hemoglobin, respectively). Because the toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event.


Asunto(s)
Infarto del Miocardio/etiología , Selenio/deficiencia , Anciano , Eritrocitos/metabolismo , Femenino , Glutatión Peroxidasa/sangre , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/metabolismo , Uñas/análisis , Factores de Riesgo , Selenio/sangre
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