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1.
Eur J Clin Nutr ; 69(4): 436-41, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25335443

RESUMEN

BACKGROUND/OBJECTIVES: The omega-3 index (the summed percentage content of eicosapentaenoic and docosahexaenoic acids in red blood cells) is associated with a lower risk of fatal coronary heart disease and sudden cardiac death. We aimed to determine which socio-demographic, behavioural or clinical factors are independently associated with the omega-3 index and the extent to which seafood consumption mediates the index's association with socio-economic status (SES). SUBJECTS/METHODS: As part of the cross-sectional MONA LISA-NUT survey (2005-2007), gas chromatography was used to analyse the red blood cell fatty acid composition in 503 French subjects aged 35-64 years. Dietary data were collected by trained dieticians via a validated food frequency questionnaire and a prospective 3-day food record. Risk factors were estimated with standardised measurements and questionnaires. SES was assessed through the self-reported educational and income tax levels. RESULTS: The mean ± s.d. omega-3 index was 6.02 ± 1.75%. In the best parsimonious predictive model (which explained 32% of the variability in the omega-3 index), age, educational level and seafood servings were significantly and positively associated with the index. In contrast, waist circumference and smoking were inversely associated with the index. In a mediation analysis that took account of all these factors, seafood servings explained about 40% of the association between educational level and the omega-3 index. Similar results were obtained for the income tax level. CONCLUSIONS: The inverse association between SES and omega-3 index is largely explained (40%) by an insufficient seafood intake. It remains to be seen which other factors mediate this association.


Asunto(s)
Dieta , Ácidos Grasos Omega-3/sangre , Población Blanca , Adulto , Índice de Masa Corporal , Estudios Transversales , Registros de Dieta , Eritrocitos/química , Femenino , Francia , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Estudios Prospectivos , Factores de Riesgo , Alimentos Marinos , Factores Socioeconómicos , Encuestas y Cuestionarios , Circunferencia de la Cintura
2.
Eur J Clin Nutr ; 67(8): 808-14, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23801096

RESUMEN

BACKGROUND/OBJECTIVES: A higher educational level is associated with a healthier diet. The goal of this study was to establish whether this association is mediated by attitudes toward healthy eating. SUBJECTS/METHODS: The cross-sectional MONA LISA-NUT study was performed in 2005-2007 on adults aged 35-64 years from northern and north-eastern France. Diet quality was assessed on the basis of a 3-day food record and a validated score based on French national dietary guidelines. Specific questions investigated attitudes toward healthy eating. Multivariate analyses were used to quantify the proportion of the educational level-diet relationship that was mediated by attitudes toward healthy eating. RESULTS: Among the 1631 subjects, favourable attitudes toward healthy eating were associated with both higher educational level and diet quality. In the mediation analysis, 'organic food consumption' explained 14% (95% confidence interval (8;24)) of the educational level-diet relationship and 'attention paid to health when buying food' explained 9% (3;16). In contrast, 'attention to food choice', 'searching for information about food' and 'perceived role of eating' were not mediators of the association between educational level and diet. In a multivariate model, the attitude items together accounted for 25% (10;45) of the relationship. The mediation was more pronounced in women than in men (37% (15;54) vs 16% (1;27), respectively) and was significant for consumption of fruits and vegetables (23% (13;37)), whole-grain food (32% (15;58)) and seafood (22% (9;55)). CONCLUSIONS: Our results suggest that poor attitudes toward healthy eating in groups with low socioeconomic status constitute an additional factor (along with cost constraints) in the choice of unhealthy foods.


Asunto(s)
Actitud Frente a la Salud , Dieta/normas , Escolaridad , Conducta Alimentaria , Adulto , Atención , Conducta de Elección , Femenino , Alimentos Orgánicos , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Política Nutricional , Factores Sexuales
3.
Int J Obes (Lond) ; 37(11): 1499-505, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23399772

RESUMEN

OBJECTIVE: Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing. DESIGN AND SUBJECTS: THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial). RESULTS: The minor allele of the index case polymorphism (rs12939700), despite having a very low frequency (4%), was significantly associated with higher body mass index (BMI) (P=0.042) in HCVR subjects. A more frequent THRA polymorphism (rs1568400) was associated with higher BMI in subjects from the population (P=0.00008 and P=0.05) after adjusting for several confounders. Rs1568400 was also strongly associated with fasting triglycerides (P dominant=3.99 × 10(-5)). In the same sample, 6 years later, age and sex-adjusted risk of developing obesity was significantly increased in GG homozygotes (odds ratio 2.93 (95% confidence interval, 1.05-6.95)). In contrast, no association between rs1568400 and BMI was observed in HCVR subjects, in whom obesity was highly prevalent. This might be explained by the presence of an interaction (P <0.001) among the rs1568400 variant, BMI and saturated fat intake. Only when saturated fat intake was high (>24.5 g d(-1)), GG carriers showed a significantly higher BMI than A carriers after controlling for energy intake and physical activity. CONCLUSIONS: THRA gene polymorphisms are associated with obesity development. This is a novel observation linking the THRA locus to metabolic phenotypes.


Asunto(s)
Hipotiroidismo/genética , Resistencia a la Insulina/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple , Receptores alfa de Hormona Tiroidea/genética , Adulto , Índice de Masa Corporal , Enfermedades Cardiovasculares/genética , Estudios Transversales , Grasas de la Dieta , Ingestión de Energía , Femenino , Francia , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Hipotiroidismo/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/etiología , Obesidad/metabolismo , Factores de Riesgo , España , Receptores alfa de Hormona Tiroidea/metabolismo
4.
Int J Obes (Lond) ; 37(5): 666-72, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22828941

RESUMEN

BACKGROUND: REV-ERBα has been shown to regulate adipogenesis and lipid metabolism as well as to link the circadian timing system to whole body metabolic homeostasis. We thus tested whether polymorphisms in REV-ERBα could be associated with metabolic phenotypes in human population samples. METHODS: We analyzed the associations between 5 REV-ERBα polymorphisms and anthropometric (body weight, body mass index (BMI), waist and hip circumferences), biochemical (plasma lipid, glucose and insulin levels) and clinical (systolic and diastolic blood pressure) variables in three population-based studies (MONICA Lille n=1155 adults, MONA LISA Lille n=1170 adults and HELENA n=1155 adolescents). We assessed in vitro, the potential influence of one REV-ERBα polymorphism in transient transfection assays using two different cell lines. RESULTS: We observed significant and consistent associations between the T minor allele of the REV-ERBα rs2071427 polymorphism (located in intron 1) and higher BMI (mean allele effect=+0.33 kg m(-2)) in the MONICA Lille (P=0.02), MONA LISA (P=0.02) and HELENA (P=0.03) studies. The odds ratios for obesity associated with this allele were 1.67 (1.00-2.79) (P=0.05) in MONICA Lille, 1.29 (1.01-1.65) (P=0.04) in MONA LISA Lille and the odds ratio for overweight was 1.48 (1.08-2.03) (P=0.01) in HELENA. In transfection experiments in human hepatocyte-derived cell lines, the REV-ERBα intron 1 directed the transcription of a luciferase reporter gene independently of the rs2071427 polymorphism. CONCLUSION: Our results suggest that the REV-ERBα rs2071427 polymorphism modulates body fat mass in both adult and young people.


Asunto(s)
Regulación de la Expresión Génica , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Antropometría , Glucemia/metabolismo , Índice de Masa Corporal , Niño , Ritmo Circadiano , Europa (Continente)/epidemiología , Femenino , Redes Reguladoras de Genes , Humanos , Insulina/sangre , Lípidos/sangre , Masculino , Persona de Mediana Edad , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/metabolismo , Obesidad/epidemiología , Obesidad/metabolismo , Oportunidad Relativa , Fenotipo
5.
Ann Cardiol Angeiol (Paris) ; 61(4): 239-44, 2012 Aug.
Artículo en Francés | MEDLINE | ID: mdl-22503754

RESUMEN

Chronic kidney disease (CKD) is a major public health issue. In France, few studies have evaluated CKD prevalence. The objective of the MONA LISA study was to estimate and to characterize CKD in three representative cross-sectional surveys in subjects aged 35-74.9 years. CKD was defined as subjects having MDRD glomerular filtration rate lower than 60 mL/min/1.73 m(2). Prevalence of CKD in MONA LISA was standardized according to the French population. A multiple logistic regression analysis was performed in order to find independent factors associated to CKD. The French estimate of CKD prevalence was 8.2% (95% confidence interval: 7.4-8.9%), that is 2,454,548 (95% confidence interval: 2,215,080-2,664,082) subjects aged 35-74.9 years. Factors significantly and independently associated to CKD were older age, hypertension and dyslipidemias. In conclusion, the MONA LISA study evaluated for the first time in France CKD prevalence in subjects aged 35-74.9 years. This prevalence probably underestimates the real CKD size due to selection bias present in every representative cross-sectional survey.


Asunto(s)
Tasa de Filtración Glomerular , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatología , Adulto , Distribución por Edad , Anciano , Intervalos de Confianza , Estudios Transversales , Dislipidemias/complicaciones , Femenino , Francia/epidemiología , Humanos , Hipertensión/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal Crónica/etiología , Medición de Riesgo , Factores de Riesgo
6.
Diabetes Metab ; 35(4): 287-92, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19447061

RESUMEN

AIM: Although the ANGPTL6 (angiopoietin-like 6) gene product is now known to be involved in the regulation of fat mass and insulin sensitivity in mice, its physiological functions in humans have yet to be determined. METHODS: Subjects from the population-based French MONICA Study (n=3402) were genotyped for single nucleotide polymorphisms (SNPs) in ANGPTL6, and associations with anthropometric or biochemical phenotypes were looked for. RESULTS: On evaluating the frequency of 17 ANGPTL6 SNPs in 100 randomly selected subjects on the basis of linkage disequilibrium mapping, four SNPs (rs6511435, rs8112063, rs11671983 and rs15723) were found to cover more than 95% of the known ANGPTL6 genetic variability. Subjects from the entire MONICA Study were then genotyped for these four SNPs. No significant association was detected for rs11671983 and rs15723. In contrast, the G allele of rs8112063 was associated with lower plasma glucose levels (P=0.009). Also, obese subjects carrying the G allele of rs6511435 had higher plasma insulin levels than AA subjects (P=0.0055). Moreover, the G allele of rs6511435 tended to be associated with a 20% higher risk of the metabolic syndrome (P=0.034). However, when false discovery rate testing (40 tests) was applied, these associations were no longer statistically significant. CONCLUSION: These findings constitute the first study in humans of ANGPTL6 genetic variability. Although there was no evidence that polymorphisms in ANGPTL6 might be significantly associated with the metabolic syndrome-related phenotypes, a weak association of these polymorphisms with these parameters cannot be excluded. Further association studies are needed to arrive at any definite conclusions.


Asunto(s)
Angiopoyetinas/genética , Síndrome Metabólico/genética , Polimorfismo de Nucleótido Simple , Proteína 6 similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Glucemia/análisis , Índice de Masa Corporal , Intervalos de Confianza , Femenino , Francia , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Insulina/sangre , Desequilibrio de Ligamiento , Lípidos/sangre , Masculino , Distribución Normal , Obesidad/genética , Oportunidad Relativa , Análisis de Regresión , Encuestas y Cuestionarios
7.
Int J Obes (Lond) ; 32(3): 421-8, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18209740

RESUMEN

CONTEXT: The metabolic syndrome is a complex and multifactorial disorder often associated with type 2 diabetes mellitus and cardiovascular diseases. The liver X receptor alpha (NR1H3) plays numerous roles in metabolic pathways involved in metabolic syndrome. OBJECTIVE: In the search for susceptibility genes to metabolic syndrome, we hypothesized that common genetic variation in NR1H3 gene influences metabolic syndrome susceptibility. DESIGN: Two large French population-based studies (n=1130 and 1160) including overall 664 individuals with and 1626 individuals without metabolic syndrome were genotyped for three polymorphisms (rs12221497, rs11039155 and rs2279239) of NR1H3. RESULTS: We found that the -6A allele of rs11039155 was consistently associated with a 30% reduction in risk of metabolic syndrome in the two independent population samples (adjusted OR (95% CI)=0.68 (0.53-0.86), P=0.001 for the combined sample). Moreover, it was associated with an increase in plasma HDL-cholesterol concentrations (P=0.02 for the combined sample). Neither rs12221497 nor rs11039155, both polymorphisms located in the 5' region of NR1H3, had significant influence on NR1H3 and ATP-binding cassette transporter A1 (ABCA1) gene expression in primary human macrophages. CONCLUSIONS: These results suggest that NR1H3 plays an important role in the HDL-cholesterol metabolism and in the genetic susceptibility to metabolic syndrome.


Asunto(s)
Proteínas de Unión al ADN/genética , Síndrome Metabólico/genética , Polimorfismo de Nucleótido Simple , Receptores Citoplasmáticos y Nucleares/genética , Adulto , HDL-Colesterol/sangre , Femenino , Francia , Ligamiento Genético , Humanos , Receptores X del Hígado , Modelos Logísticos , Masculino , Síndrome Metabólico/sangre , Persona de Mediana Edad , Receptores Nucleares Huérfanos , Riesgo
9.
Mol Psychiatry ; 12(9): 870-80, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17579612

RESUMEN

Variations in the S100beta gene may be instrumental in producing a continuum from mild cognitive decline to overt dementia. After screening 25 single nucleotide polymorphisms (SNPs) in S100beta, we observed association of the rs2300403 intron 2 SNP with poorer cognitive function in three independent populations. Moreover, we detected a significant association of this SNP with increased risk of developing dementia or Alzheimer's disease (AD) in six independent populations, especially in women and in the oldest. Furthermore, we characterised a new primate-specific exon within intron 2 (the corresponding mRNA isoform was called S100beta2). S100beta2 expression was increased in AD brain compared with controls, and the rs2300403 SNP was associated with elevated levels of S100beta2 mRNA in AD brains, especially in women. Therefore, this genetic variant in S100beta increases the risk of low cognitive performance and dementia, possibly by favouring a splicing event increasing S100beta2 isoform expression in the brain.


Asunto(s)
Trastornos del Conocimiento/etiología , Demencia/complicaciones , Demencia/genética , Predisposición Genética a la Enfermedad , Factores de Crecimiento Nervioso/genética , Polimorfismo de Nucleótido Simple , Proteínas S100/genética , Factores de Edad , Anciano , Anciano de 80 o más Años , Planificación en Salud Comunitaria , Dinamarca/epidemiología , Enfermedades en Gemelos , Femenino , Evaluación Geriátrica , Humanos , Masculino , Pruebas Neuropsicológicas , Estudios Retrospectivos , Subunidad beta de la Proteína de Unión al Calcio S100 , Índice de Severidad de la Enfermedad , Factores Sexuales , Estudios en Gemelos como Asunto
10.
J Neurol Neurosurg Psychiatry ; 75(3): 377-81, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14966150

RESUMEN

BACKGROUND: The NOTCH4 gene is located at 6p21.3, a site shown in several studies to have significant linkage with Alzheimer's disease. OBJECTIVE: To investigate the potential impact of two polymorphisms within this gene on the risk of developing Alzheimer's disease. METHODS: Genotyping of promoter and 5'-UTR polymorphisms was done in Scottish, English, and French populations. The potential functionality of the 5'-UTR polymorphism was assessed by testing its impact on A beta load in Alzheimer brains and also by undertaking electrophoretic mobility shift assays and transfection experiments. RESULTS: No association of the Notch4 polymorphisms alone with the disease was observed in any of the populations. However, an interaction of the 5'-UTR C/T polymorphism with the epsilon 4 allele of the APOE gene was detected in United Kingdom populations but not in the French. No relation between the 5'-UTR polymorphism and A beta loads was detected overall or in the presence or absence of the epsilon 4 allele. No DNA protein specific binding was found with proteins from neuroblastoma, glioma, or astrocytoma cells, and no allele dependent transcriptional activity was detected. CONCLUSIONS: No association between two NOTCH4 polymorphisms alone and Alzheimer's disease was observed in the three populations, but there was evidence of an increased risk associated with the 5'-UTR CC genotype in epsilon 4 bearers in the United Kingdom. As no functionality for this polymorphism could be determined, it is likely that the interaction is spurious or results from a linkage disequilibrium of this 5'-UTR polymorphism with another marker elsewhere in the 6p21.3 locus.


Asunto(s)
Enfermedad de Alzheimer/genética , Cromosomas Humanos Par 6 , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Proteínas Proto-Oncogénicas/genética , Receptores de Superficie Celular , Regiones no Traducidas 5'/genética , Edad de Inicio , Anciano , Enfermedad de Alzheimer/fisiopatología , Estudios Transversales , Inglaterra , Femenino , Francia , Genética de Población , Genotipo , Humanos , Complejo Mayor de Histocompatibilidad , Masculino , Persona de Mediana Edad , Receptor Notch4 , Receptores Notch , Factores de Riesgo , Escocia
11.
Ann Nutr Metab ; 48(1): 43-50, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-14646340

RESUMEN

AIMS: Metabolic disorders depend on genetic, hormonal and environmental factors, whose relations may differ between genders. Therefore, we compared the contribution of metabolic disorders to the metabolic syndrome in women and men. METHODS: To this end, we used a hierarchical classification statistical method to classify subjects into similarity groups according to clinical and biological parameters. Data were collected from 3,508 men and women aged 35-64 years, from a cardiovascular disease survey. RESULTS: In both women and men, hierarchical classification identified a cluster corresponding to the metabolic syndrome representing 14 and 15% of the women's and men's sample, respectively. In women, elevated body weight (women's Z-score: 1.59 vs. men's Z-score: 1.29; p < 0.005), waist girth (1.62 vs. 1.30; p < 0.001) and low HDL cholesterol (-0.95 vs. -0.75; p < 0.05) were significantly larger contributors to the metabolic syndrome than in men. In contrast, systolic (0.59 vs. 0.95; p < 0.0001) and diastolic (0.55 vs. 0.99; p < 0.0001) blood pressure and apolipoprotein B (0.51 vs. 0.71; p < 0.0001) contributed significantly less in women than in men. Finally, insulin (n.s.), glucose (n.s.), triglycerides (n.s.) and LDL-cholesterol (n.s.) contributions were not different between genders. CONCLUSION: These results are consistent with the concept that a clustering of metabolic disorders occurs frequently in both women and men. However, the contribution of several metabolic disorders to the metabolic syndrome is different in men and women. This finding supports the concept that different criteria are necessary to define the metabolic syndrome in women and men.


Asunto(s)
Hiperlipidemias/sangre , Hipertensión/sangre , Resistencia a la Insulina/fisiología , Síndrome Metabólico/sangre , Obesidad/sangre , Caracteres Sexuales , Adulto , Apolipoproteínas B/sangre , Constitución Corporal/fisiología , Peso Corporal/fisiología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Análisis por Conglomerados , Femenino , Humanos , Hiperlipidemias/etiología , Hipertensión/etiología , Masculino , Síndrome Metabólico/clasificación , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , Obesidad/fisiopatología , Triglicéridos/sangre
12.
J Med Genet ; 40(6): 424-30, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12807963

RESUMEN

Although possession of the epsilon 4 allele of the apolipoprotein E gene appears to be an important biological marker for Alzheimer's disease (AD) susceptibility, strong evidence indicates that at least one additional risk gene exists on chromosome 12. Here, we describe an association of the 3'-UTR +1073 C/T polymorphism of the OLR1 (oxidised LDL receptor 1) on chromosome 12 with AD in French sporadic (589 cases and 663 controls) and American familial (230 affected sibs and 143 unaffected sibs) populations. The age and sex adjusted odds ratio between the CC+CT genotypes versus the TT genotypes was 1.56 (p=0.001) in the French sample and 1.92 (p=0.02) in the American sample. Furthermore, we have discovered a new T/A polymorphism two bases upstream of the +1073 C/T polymorphism. This +1071 T/A polymorphism was not associated with the disease, although it may weakly modulate the impact of the +1073 C/T polymorphism. Using 3'-UTR sequence probes, we have observed specific DNA protein binding with nuclear proteins from lymphocyte, astrocytoma, and neuroblastoma cell lines, but not from the microglia cell line. This binding was modified by both the +1071 T/A and +1073 C/T polymorphisms. In addition, a trend was observed between the presence or absence of the +1073 C allele and the level of astrocytic activation in the brain of AD cases. However, Abeta(40), Abeta(42), Abeta total, and Tau loads or the level of microglial cell activation were not modulated by the 3'-UTR OLR1 polymorphisms. Finally, we assessed the impact of these polymorphisms on the level of OLR1 expression in lymphocytes from AD cases compared with controls. The OLR1 expression was significantly lower in AD cases bearing the CC and CT genotypes compared with controls with the same genotypes. In conclusion, our data suggest that genetic variation in the OLR1 gene may modify the risk of AD.


Asunto(s)
Regiones no Traducidas 3'/genética , Enfermedad de Alzheimer/genética , Polimorfismo Genético/genética , Receptores de LDL/genética , Factores de Edad , Edad de Inicio , Anciano , Alelos , Enfermedad de Alzheimer/epidemiología , Encéfalo/patología , Cromosomas Humanos Par 12/genética , ADN/sangre , ADN/genética , ADN de Neoplasias/genética , Femenino , Francia/epidemiología , Genotipo , Haplotipos/genética , Humanos , Linfocitos/química , Masculino , Oxidación-Reducción , Receptores de LDL Oxidadas , Receptores Depuradores de Clase E , Factores Sexuales , Células Tumorales Cultivadas , Estados Unidos/epidemiología
13.
Mol Psychiatry ; 8(4): 413-22, 363, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12740599

RESUMEN

Islet-brain1 (IB1) or c-Jun NH2 terminal kinase interacting protein-1 (JIP-1), the product of the MAPK8IP1 gene, functions as a neuronal scaffold protein to allow signalling specificity. IB1/JIP-1 interacts with many cellular components including the reelin receptor ApoER2, the low-density lipoprotein receptor-related protein (LRP), kinesin and the Alzheimer's amyloid precursor protein. Coexpression of IB1/JIP-1 with other components of the c-Jun NH2 terminal-kinase (JNK) pathway activates the JNK activity; conversely, selective disruption of IB1/JIP-1 in mice reduces the stress-induced apoptosis of neuronal cells. We therefore hypothesized that IB1/JIP-1 is a risk factor for Alzheimer's disease (AD). By immunocytochemistry, we first colocalized the presence of IB1/JIP-1 with JNK and phosphorylated tau in neurofibrillary tangles. We next identified a -499A>G polymorphism in the 5' regulatory region of the MAPK8IP1 gene. In two separate French populations the -499A>G polymorphism of MAPK8IP1 was not associated with an increased risk to AD. However, when stratified on the +766C>T polymorphism of exon 3 of the LRP gene, the IB1/JIP-1 polymorphism was strongly associated with AD in subjects bearing the CC genotype in the LRP gene. The functional consequences of the -499A>G polymorphism of MAPK8IP1 was investigated in vitro. In neuronal cells, the G allele increased transcriptional activity and was associated with an enhanced binding activity. Taken together, these data indicate that the increased transcriptional activity in the presence of the G allele of MAPK8IP1 is a risk factor to the onset of in patients bearing the CC genotype of the LRP gene.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Enfermedad de Alzheimer/genética , Proteínas Portadoras/genética , Proteínas Nucleares/genética , Regiones Promotoras Genéticas , Transactivadores/genética , Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/patología , Autopsia , Secuencia de Bases , Encéfalo/patología , Cognición , Cartilla de ADN , Francia , Variación Genética , Humanos , Neuroblastoma , Proteína Reelina , Transfección , Células Tumorales Cultivadas
14.
Neurosci Lett ; 335(2): 75-8, 2002 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-12459502

RESUMEN

A possible association of the human leucocyte antigen (HLA)-A2 allele with increased susceptibility to Alzheimer's disease (AD) has been the subject of debate for more than 20 years. We compared the presence of the HLA-A2 allele in a sample from the French population composed of 451 patients and 477 controls. There was no evidence of an association of this allele with increased risk of AD. Moreover, no effect was observed when we stratified the case-control sample on gender, age of onset or presence of an APOE epsilon4 allele. We conclude that HLA-A2 allele is not a major risk factor for sporadic AD.


Asunto(s)
Alelos , Enfermedad de Alzheimer/genética , Antígeno HLA-A2/genética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/etiología , Cromosomas Humanos Par 21 , Femenino , Francia , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo Genético
15.
J Neural Transm (Vienna) ; 109(7-8): 1023-7, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12111439

RESUMEN

Recently, a polymorphism located in the promoter of the presenilin 1 gene was associated with early-onset Alzheimer disease (EOAD). To determine if this polymorphism is also a risk factor for late-onset Alzheimer's disease (LOAD), we analysed its potential impact in a French population of LOAD patients only. Genotype and allelic distributions of the -48CT polymorphism were similar for controls and AD patients. Our result suggests that this polymorphism may not influence the development of LOAD. Other studies need to be undertaken to confirm this association restricting the impact of this polymorphism to EOAD patients.


Asunto(s)
Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Proteínas de la Membrana/genética , Polimorfismo Genético/genética , Edad de Inicio , Anciano , Anciano de 80 o más Años , Alelos , Apolipoproteínas E/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Presenilina-1 , Regiones Promotoras Genéticas/genética , Valores de Referencia
16.
J Neurol Neurosurg Psychiatry ; 73(1): 62-4, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12082048

RESUMEN

BACKGROUND: There is evidence that inflammatory processes may contribute to the development of Alzheimer's disease through production of cytokines and free radicals that damage neurones. A recent study has shown that transforming growth factor beta1 (TGF-beta1) signalling in astrocytes promotes Abeta production and could play a critical role in the formation of amyloid plaques in the brain. OBJECTIVES: To explore the impact of the -800 and -509 TGF-beta1 promoter polymorphisms and the +25 polymorphism on the risk of occurrence of Alzheimer's disease in a large population of sporadic cases and controls, and on the amyloid beta (Abeta) load in the brains of Alzheimer patients. METHODS: The TGF-beta1 genotypes of the three polymorphisms were determined in 678 sporadic Alzheimer's disease patients and 667 controls. They were also characterised, along with Abeta load, in the brains of 81 necropsy confirmed Alzheimer patients. RESULTS: No significant variations in the distribution of the genotypes and haplotypes were observed between Alzheimer patients and controls, or in the amount of Abeta deposition. CONCLUSIONS: These results do not suggest an influence of genetic variability at the TGF-beta1 gene locus on the occurrence of Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer/genética , Polimorfismo Genético , Factor de Crecimiento Transformador beta/genética , Anciano , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Factor de Crecimiento Transformador beta1
17.
J Epidemiol Community Health ; 56(1): 24-8, 2002 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11801616

RESUMEN

STUDY OBJECTIVE: Prospective studies have shown a consistent relation between alcohol consumption and decreasing incidence of coronary artery disease. The protective effect of alcohol could be mediated through increased levels of HDL cholesterol (HDL-c). The aim of this study was to examine the relation between blood lipid levels and the consumption of different types of alcoholic beverages among 1581 men and 1535 women. DESIGN: Data from representative cross sectional surveys (1994-1997) in three different regions of France were used. The consumption of the different types of alcohol was quantified using a recall method according to a typical weekly consumption. MAIN RESULTS: The median daily alcohol intake was 24 g for men and 4 g for women. After adjustment for confounders, total alcohol showed a positive and significant association with HDL-c and triglycerides (TG) in both sexes. In multivariate analysis, wine was positively associated with HDL-c. Beer was positively associated with HDL-c in men and with triglycerides in men and women. When taking drinking patterns into account, wine drinkers had higher HDL-c levels than non-wine drinkers. Differences became non-significant after adjustment for confounders and particularly for socioeconomic parameters. CONCLUSIONS: In a French population sample, total alcohol was positively associated with HDL-c and triglycerides. The specific influence of any particular alcoholic beverage on blood lipids was not clearly demonstrated but wine preference found in a group with higher lifestyle standards was associated with a more favourable blood lipid profile.


Asunto(s)
Consumo de Bebidas Alcohólicas/sangre , Bebidas Alcohólicas/clasificación , HDL-Colesterol/sangre , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Análisis de Varianza , Estudios Transversales , Femenino , Francia/epidemiología , Humanos , Estilo de Vida , Modelos Lineales , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/prevención & control , Triglicéridos/sangre
18.
Diabetes Metab ; 27(4 Pt 1): 503-9, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11547225

RESUMEN

OBJECTIVES: To assess the effect of parental histories of cardiovascular risk factors on risk factor clusters (RFC) in representative samples from three French populations (MONICA centers of Lille, Strasbourg, Toulouse). MATERIAL AND METHODS: In a representative cross-sectional study, we screened 1,291 males and 1,264 females, aged 35-64 years. Subjects were defined as RFC cases when they were affected by at least 2 disorders among, hypertension (systolic or diastolic blood pressure >=140/90 mmHg and/or antihypertensive drug), diabetes (physician-diagnosed diabetes and/or glycemia >=7.0 mmol/l and/or hypoglycemic drug), and dyslipidemia (triglycerides > 2.26 mmol/l and/or HDL-cholesterol<0.9 mmol/l in men and<1.2 mmol/l in women). Nineteen percent of the subjects were RFC cases. Parental histories of cardiovascular risk factors (hypertension, diabetes, hyperlipidemia) were positive if they were under 65. About 29% of the subjects had at least one parental history of risk factor. RESULTS: After adjustment for sex, age, educational level, sedentary lifestyle, alcohol consumption, body mass index, LDL cholesterol and center, parental histories of cardiovascular risk factors were significantly associated with the RFC. One, two, or at least three parental histories were significantly associated with increased odds of being RFC cases (adjusted OR 1.39 95% CI [1.05-1.82], 2.90 95% CI [1.91-4.40], 2.93 95% CI [1.41-6.08]). Furthermore, a maternal-only history vs a paternal-only history of hypertension or diabetes was associated with strong odds of being an RFC case. CONCLUSION: At least a single cardiovascular risk factor in parents was significantly associated with RFC in offspring, independently of environmental parameters.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Adulto , Distribución por Edad , Consumo de Bebidas Alcohólicas/epidemiología , Constitución Corporal , Estudios Transversales , Diabetes Mellitus/genética , Femenino , Francia/epidemiología , Humanos , Hiperlipidemias/genética , Hipertensión/genética , Estilo de Vida , Masculino , Persona de Mediana Edad , Núcleo Familiar , Padres , Factores de Riesgo , Encuestas y Cuestionarios
19.
Int J Obes Relat Metab Disord ; 25(7): 1012-7, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11443500

RESUMEN

OBJECTIVE: To assess whether the -455 and -482 mutations in APOC-III gene insulin response element affect the relationships between plasma insulin and triglyceride-rich lipoprotein levels. DESIGN: Population-based studies. SUBJECTS: The population sample was composed of 983 subjects (485 men and 498 women), aged between 35 and 65 y, randomly sampled from the electoral rolls in Northern France and stratified on gender and 10 y age groups. MEASUREMENTS: Plasma triglyceride, apolipoprotein C-III, apoB, LpC-III:B and LpE:B lipoprotein particles and insulin levels were measured. Two polymorphisms in APOC-III gene insulin response element (T-->C at -455 and/or C-->T at -482) were determined. RESULTS: Plasma insulin was positively correlated to triglyceride levels (P<0.0001), apo C-III (P<0.003), LpC-III:B (P<0.0001), apoB (P<0.0001) and LpE:B (P<0.0001). This association differed significantly according to APOC-III insulin response element polymorphisms. The relationship between insulin and LpC-III:B (P<0.02) or apoB (P<0.02) was greater in women bearing the C allele of -455 than the T allele. Similarly, the relationship between insulin and LpC-III:B (P<0.02) or LpE:B (P<0.05) was greater in women bearing the T allele of -482 than the C allele. There was no evidence for any effect in men. CONCLUSION: These results suggest that the relationship between plasma insulin and triglyceride-rich lipoprotein levels is partly influenced by polymorphisms in APOC-III insulin response element.


Asunto(s)
Apolipoproteínas C/genética , Insulina/sangre , Polimorfismo Genético , Triglicéridos/sangre , Adulto , Anciano , Alelos , Apolipoproteína C-III , Apolipoproteínas/sangre , Apolipoproteínas/genética , Femenino , Francia , Humanos , Insulina/genética , Masculino , Persona de Mediana Edad , Factores Sexuales , Encuestas y Cuestionarios , Triglicéridos/genética
20.
Diabetes Metab ; 27(3): 347-58, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11431600

RESUMEN

OBJECTIVES: The aim of this study was to determine the prevalence of type 2 diabetes and impaired fasting glucose (IFG) in a population-based sample of 3 508 subjects, aged 35-64 years, participating in the French MONICA population survey from 1995 to 1997 in three French regions: the Urban Community of Lille, the Bas-Rhin and the Haute-Garonne. MATERIAL AND METHODS: Previously diagnosed type 2 diabetes is defined by the current use of oral hypoglycaemic treatment and newly diagnosed subjects by fasting plasma glucose (FPG) > or =7.0 mmol/L according to the ADA 1997 recommendations. IFG was determined by 6.1< or =FPG< or =6.9 mmol/L. Adjusted prevalences are calculated according to the French 1990 census data. RESULTS: Type 2 diabetes adjusted prevalence is 5.1% [4.1-6.1] in women and 7.3% [6.1-8.4] in men while IFG adjusted prevalence is 5.2% [4.2-6.2] and 11.8% [10.3-13.4] respectively. Prevalences of type 2 diabetes and IFG are both significantly higher in men than in women. This trend appears in any age group for IFG, but is only observed in 55-64 year-old subjects for type 2 diabetes. The reduction of the FPG threshold to screen diabetes mellitus from 7.8 to 7.0 mmol/L according to the ADA recommendations results in a 2.2-fold increase in the number of newly diagnosed diabetic subjects, screened by one FPG measurement, in our population-based sample. CONCLUSIONS: The MONICA population survey confirms that type 2 diabetes represents a major health care problem in France and underlines the influence of gender on the prevalence of both type 2 diabetes and IFG in the French middle-aged population.


Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Intolerancia a la Glucosa/epidemiología , Adulto , Distribución por Edad , Demografía , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Francia/epidemiología , Encuestas Epidemiológicas , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Prevalencia , Población Rural/estadística & datos numéricos , Factores Socioeconómicos , Población Urbana/estadística & datos numéricos
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