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1.
Artigo em Inglês | MEDLINE | ID: mdl-34584012

RESUMO

BACKGROUND AND OBJECTIVES: To investigate the genetic determinants of the most common type of antibody-mediated autoimmune encephalitis, anti-NMDA receptor (anti-NMDAR) encephalitis. METHODS: We performed a genome-wide association study in 178 patients with anti-NMDAR encephalitis and 590 healthy controls, followed by a colocalization analysis to identify putatively causal genes. RESULTS: We identified 2 independent risk loci harboring genome-wide significant variants (p < 5 × 10-8, OR ≥ 2.2), 1 on chromosome 15, harboring only the LRRK1 gene, and 1 on chromosome 11 centered on the ACP2 and NR1H3 genes in a larger region of high linkage disequilibrium. Colocalization signals with expression quantitative trait loci for different brain regions and immune cell types suggested ACP2, NR1H3, MADD, DDB2, and C11orf49 as putatively causal genes. The best candidate genes in each region are LRRK1, encoding leucine-rich repeat kinase 1, a protein involved in B-cell development, and NR1H3 liver X receptor alpha, a transcription factor whose activation inhibits inflammatory processes. DISCUSSION: This study provides evidence for relevant genetic determinants of antibody-mediated autoimmune encephalitides outside the human leukocyte antigen (HLA) region. The results suggest that future studies with larger sample sizes will successfully identify additional genetic determinants and contribute to the elucidation of the pathomechanism.

2.
Traffic ; 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34564930

RESUMO

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the brain. The continuous trafficking of AMPARs into and out of synapses is a core feature of synaptic plasticity, which is considered as the cellular basis of learning and memory. The molecular mechanisms underlying the postsynaptic AMPAR trafficking, however, are still not fully understood. In this work, we demonstrate that the protein kinase D (PKD) family promotes basal and activity-induced AMPAR endocytosis in primary hippocampal neurons. Pharmacological inhibition of PKD increased synaptic levels of GluA1-containing AMPARs, slowed down their endocytic trafficking and increased neuronal network activity. By contrast, ectopic expression of constitutive active PKD decreased the synaptic level of AMPARs, while increasing their colocalization with early endosomes. Our results thus establish an important role for PKD in the regulation of postsynaptic AMPAR trafficking during synaptic plasticity.

3.
J Clin Periodontol ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34409643

RESUMO

AIMS: Various studies have reported that young European women are more likely to develop early-onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the increased prevalence and severity. MATERIALS AND METHODS: Using the case-only design, we tested for differences in genetic effects between men and women in 896 North-West European early-onset cases, using imputed genotypes from the OmniExpress genotyping array. Population-representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population. RESULTS: In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13). CONCLUSIONS: Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter-sex phenotypic variation in early-onset periodontitis.

5.
Ophthalmologe ; 118(8): 777-786, 2021 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-34324055

RESUMO

BACKGROUND: Orbital inflammatory disease encompasses a spectrum of disorders. Idiopathic orbital inflammation (IOI) is often a diagnosis of exclusion, which needs to be differentiated from infections, systemic inflammatory disease, and neoplasms. IOI includes anterior inflammation with dacryoadenitis, myositis, perineuritis of the optic nerve, periscleritis, diffuse sclerosing inflammation, and orbital apex inflammation. OBJECTIVE: A differential diagnostic overview of IOI is presented, including its subcategories, diagnosis, and treatment. CONCLUSION: The diagnosis of IOI is often made by exclusion with typical clinical findings, CT and MRI scans, and pathology. Treatment includes corticosteroids, immunomodulators, immunosuppressants, and radiotherapy.


Assuntos
Doenças Orbitárias , Pseudotumor Orbitário , Diagnóstico Diferencial , Humanos , Inflamação/diagnóstico , Imageamento por Ressonância Magnética , Doenças Orbitárias/diagnóstico , Pseudotumor Orbitário/diagnóstico , Pseudotumor Orbitário/tratamento farmacológico
6.
J Cell Mol Med ; 25(16): 8047-8061, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34165249

RESUMO

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

7.
Front Immunol ; 12: 684326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177931

RESUMO

Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells via interaction with HLA ligands. KIR genes, including KIR2DS1, KIR3DL1, and KIR3DS1 have previously been implicated in psoriasis susceptibility. However, these previous studies were constrained to small sample sizes, in part due to the time and expense required for direct genotyping of KIR genes. Here, we implemented KIR*IMP to impute KIR copy number from single-nucleotide polymorphisms (SNPs) on chromosome 19 in the discovery cohort (n=11,912) from the PAGE consortium, University of California San Francisco, and the University of Dundee, and in a replication cohort (n=66,357) from Kaiser Permanente Northern California. Stratified multivariate logistic regression that accounted for patient ancestry and high-risk HLA alleles revealed that KIR2DL2 copy number was significantly associated with psoriasis in the discovery cohort (p ≤ 0.05). The KIR2DL2 copy number association was replicated in the Kaiser Permanente replication cohort. This is the first reported association of KIR2DL2 copy number with psoriasis and highlights the importance of KIR genetics in the pathogenesis of psoriasis.

8.
Am J Clin Nutr ; 114(2): 441-449, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33964858

RESUMO

BACKGROUND: Plant-rich diets are associated with lower cardiometabolic risks and longer survival in the general population, but their association with mortality in cancer survivors is still unclear. OBJECTIVES: We aimed to examine the associations of 3 postdiagnostic plant-based diet indices with all-cause mortality in omnivorous long-term colorectal cancer (CRC) survivors. METHODS: Diet was assessed with FFQs at a median of 6 years after diagnosis in 1404 CRC survivors (56% male; median age, 69 years) in a Northern German prospective cohort study. An overall, a healthful plant-based, and an unhealthful plant-based diet index were derived by scoring intakes of animal foods reversely and intakes of healthy (whole grains, vegetables, fruits, legumes, nuts, oils, tea/coffee) and less healthy plant foods (refined grains, fruit juices, sugar-sweetened beverages, potatoes, sweets/desserts) positively or reversely, depending on the index. Vital status follow-up was conducted via population registries. Cox proportional hazards regression was applied to estimate HRs for all-cause mortality according to plant-based diet adherence. RESULTS: Within 7 years (median) after diet assessment, 204 deaths occurred. The overall plant-based diet index displayed a significant, inverse association with all-cause mortality (HR per 10-point increase in diet index, 0.72; 95% CI, 0.57-0.91). Although not statistically significant, higher healthful plant-based diet scores showed a strong tendency towards lower mortality (HR, 0.82; 95% CI, 0.67-1.01). The unhealthful plant-based diet index was associated with higher mortality, but lost statistical significance after multivariable adjustment (HR, 1.19; 95% CI, 0.96-1.48). A subgroup analysis revealed that the tendency towards a positive association of the unhealthful plant-based diet with mortality was restricted to less physically active individuals (<95 metabolic equivalent of task hours/week). CONCLUSIONS: An overall plant-based diet was inversely associated with all-cause mortality in long-term CRC survivors. However, more research is needed to further disentangle the impacts of different qualities of plant-based diets on cancer survivors' health.


Assuntos
Sobreviventes de Câncer , Neoplasias Colorretais , Dieta Vegetariana , Proteínas na Dieta , Mortalidade , Idoso , Animais , Dieta , Comportamento Alimentar , Feminino , Humanos , Masculino , Carne , Pessoa de Meia-Idade , Fatores de Tempo
9.
Orphanet J Rare Dis ; 16(1): 228, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011352

RESUMO

Bullous pemphigoid (BP) is the most common autoimmune skin blistering disease characterized by autoimmunity against the hemidesmosomal proteins BP180, type XVII collagen, and BP230. To elucidate the genetic basis of susceptibility to BP, we performed the first genome-wide association study (GWAS) in Germans. This GWAS was combined with HLA locus targeted sequencing in an additional independent BP cohort. The strongest association with BP in Germans tested in this study was observed in the two HLA loci, HLA-DQA1*05:05 and HLA-DRB1*07:01. Further studies with increased sample sizes and complex studies integrating multiple pathogenic drivers will be conducted.


Assuntos
Cadeias alfa de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Penfigoide Bolhoso , Alelos , Autoanticorpos , Autoantígenos , Estudo de Associação Genômica Ampla , Alemanha , Humanos , Colágenos não Fibrilares , Penfigoide Bolhoso/genética
10.
Front Immunol ; 12: 614653, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815372

RESUMO

Chronic inflammatory diseases (CID) are emerging disorders which do not only affect specific organs with respective clinical symptoms but can also affect various aspects of life, such as emotional distress, anxiety, fatigue and quality of life. These facets of chronic disease are often not recognized in the therapy of CID patients. Furthermore, the symptoms and patient-reported outcomes often do not correlate well with the actual inflammatory burden. The discrepancy between patient-reported symptoms and objectively assessed disease activity can indeed be instructive for the treating physician to draw an integrative picture of an individual's disease course. This poses a challenge for the design of novel, more comprehensive disease assessments. In this mini-review, we report on the currently available patient-reported outcomes, the unmet needs in the field of chronic inflammatory diseases and the challenges of addressing these.


Assuntos
Inflamação/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Doença Crônica , Comorbidade , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Inflamação/terapia , Participação do Paciente , Relações Médico-Paciente , Padrões de Prática Médica , Medicina de Precisão , Vigilância em Saúde Pública , Fatores de Risco
11.
Gut ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888516

RESUMO

OBJECTIVE: Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. DESIGN: We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry. RESULTS: We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix. CONCLUSION: HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.

13.
Gastroenterology ; 160(5): 1784-1798.e0, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33387530

RESUMO

BACKGROUND & AIMS: To influence host and disease phenotype, compositional microbiome changes, which have been demonstrated in patients with primary sclerosing cholangitis (PSC), must be accompanied by functional changes. We therefore aimed to characterize the genetic potential of the gut microbiome in patients with PSC compared with healthy controls (HCs) and patients with inflammatory bowel disease (IBD). METHODS: Fecal DNA from 2 cohorts (1 Norwegian and 1 German), in total comprising 136 patients with PSC (58% with IBD), 158 HCs, and 93 patients with IBD without PSC, were subjected to metagenomic shotgun sequencing, generating 17 billion paired-end sequences, which were processed using HUMAnN2 and MetaPhlAn2, and analyzed using generalized linear models and random effects meta-analyses. RESULTS: Patients with PSC had fewer microbial genes compared with HCs (P < .0001). Compared with HCs, patients with PSC showed enrichment and increased prevalence of Clostridium species and a depletion of, for example, Eubacterium spp and Ruminococcus obeum. Patients with PSC showed marked differences in the abundance of genes related to vitamin B6 synthesis and branched-chain amino acid synthesis (Qfdr < .05). Targeted metabolomics of plasma from an independent set of patients with PSC and controls found reduced concentrations of vitamin B6 and branched-chain amino acids in PSC (P < .0001), which strongly associated with reduced liver transplantation-free survival (log-rank P < .001). No taxonomic or functional differences were detected between patients with PSC with and without IBD. CONCLUSIONS: The gut microbiome in patients with PSC exhibits large functional differences compared with that in HCs, including microbial metabolism of essential nutrients. Alterations in related circulating metabolites associated with disease course, suggesting that microbial functions may be relevant for the disease process in PSC.


Assuntos
Bactérias/metabolismo , Colangite Esclerosante/microbiologia , Microbioma Gastrointestinal , Metaboloma , Metagenoma , Adolescente , Adulto , Idoso , Bactérias/genética , Estudos de Casos e Controles , Colangite Esclerosante/sangue , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/cirurgia , Estudos Transversais , Disbiose , Fezes/microbiologia , Feminino , Alemanha , Humanos , Transplante de Fígado , Masculino , Metabolômica , Metagenômica , Pessoa de Meia-Idade , Noruega , Filogenia , Intervalo Livre de Progressão , Adulto Jovem
14.
J Cardiovasc Magn Reson ; 23(1): 2, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33390171

RESUMO

BACKGROUND: The association of longitudinal trajectories of cardiovascular risk factors with cardiovascular magnetic resonance (CMR)-measures of cardiac structure and function in the community is not well known. Therefore we aimed to relate risk factor levels from different examination cycles to CMR-measures of the left ventricle (LV) and right ventricle in a population-based cohort. METHODS: We assessed conventional cardiovascular disease risk factors in 349 participants (143 women; aged 25-59 years) at three examination cycles (Exam 1 [baseline], at Exam 2 [7-years follow-up] and at Exam 3 [14-years follow-up]) of the KORA S4 cohort and related single-point measurements of individual risk factors and longitudinal trajectories of these risk factors to various CMR-measures obtained at Exam 3. RESULTS: High levels of diastolic blood pressure, waist circumference, and LDL-cholesterol at the individual exams were associated with worse cardiac function and structure. Trajectory clusters representing higher levels of the individual risk factors were associated with worse cardiac function and structure compared to low risk trajectory clusters of individual risk factors. Multivariable (combining different risk factors) trajectory clusters were associated with different cardiac parameters in a graded fashion (e.g. decrease of LV stroke volume for middle risk cluster ß = - 4.91 ml/m2, 95% CI - 7.89; - 1.94, p < 0.01 and high risk cluster ß = - 7.00 ml/m2, 95% CI - 10.73; - 3.28, p < 0.001 compared to the low risk cluster). The multivariable longitudinal trajectory clusters added significantly to explain variation in CMR traits beyond the multivariable risk profile obtained at Exam 3. CONCLUSIONS: Cardiovascular disease risk factor levels, measured over a time period of 14 years, were associated with CMR-derived measures of cardiac structure and function. Longitudinal multivariable trajectory clusters explained a greater proportion of the inter-individual variation in cardiac traits than multiple risk factor assessed contemporaneous with the CMR exam.


Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Adulto , Idoso , Pressão Sanguínea , Composição Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Alemanha/epidemiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Tempo , Função Ventricular Esquerda , Função Ventricular Direita
15.
J Gerontol A Biol Sci Med Sci ; 76(5): 786-795, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33491046

RESUMO

Despite enormous research efforts, the genetic component of longevity has remained largely elusive. The investigation of common variants, mainly located in intronic or regulatory regions, has yielded only little new information on the heritability of the phenotype. Here, we performed a chip-based exome-wide association study investigating 62 488 common and rare coding variants in 1248 German long-lived individuals, including 599 centenarians and 6941 younger controls (age < 60 years). In a single-variant analysis, we observed an exome-wide significant association between rs1046896 in the gene fructosamine-3-kinase-related-protein (FN3KRP) and longevity. Noteworthy, we found the longevity allele C of rs1046896 to be associated with an increased FN3KRP expression in whole blood; a database look-up confirmed this effect for various other human tissues. A gene-based analysis, in which potential cumulative effects of common and rare variants were considered, yielded the gene phosphoglycolate phosphatase (PGP) as another potential longevity gene, though no single variant in PGP reached the discovery p-value (1 × 10E-04). Furthermore, we validated the previously reported longevity locus cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1). Replication of our results in a French longevity cohort was only successful for rs1063192 in CDKN2B-AS1. In conclusion, we identified 2 new potential candidate longevity genes, FN3KRP and PGP which may influence the phenotype through their role in metabolic processes, that is, the reverse glycation of proteins (FN3KRP) and the control of glycerol-3-phosphate levels (PGP).


Assuntos
Longevidade/genética , Monoéster Fosfórico Hidrolases/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Exoma/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade
16.
Nat Genet ; 53(2): 147-155, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33462482

RESUMO

The intestinal microbiome is implicated as an important modulating factor in multiple inflammatory1,2, neurologic3 and neoplastic diseases4. Recent genome-wide association studies yielded inconsistent, underpowered and rarely replicated results such that the role of human host genetics as a contributing factor to microbiome assembly and structure remains uncertain5-11. Nevertheless, twin studies clearly suggest host genetics as a driver of microbiome composition11. In a genome-wide association analysis of 8,956 German individuals, we identified 38 genetic loci to be associated with single bacteria and overall microbiome composition. Further analyses confirm the identified associations of ABO histo-blood groups and FUT2 secretor status with Bacteroides and Faecalibacterium spp. Mendelian randomization analysis suggests causative and protective effects of gut microbes, with clade-specific effects on inflammatory bowel disease. This holistic investigative approach of the host, its genetics and its associated microbial communities as a 'metaorganism' broaden our understanding of disease etiology, and emphasize the potential for implementing microbiota in disease treatment and management.


Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Microbioma Gastrointestinal/genética , Bacteroides/genética , Faecalibacterium/genética , Fucosiltransferases/genética , Estudo de Associação Genômica Ampla , Alemanha , Humanos , Lactase/genética , Desequilíbrio de Ligação , Análise da Randomização Mendeliana
17.
Mov Disord ; 36(2): 449-459, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33107653

RESUMO

BACKGROUND: Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by intracellular accumulations of α-synuclein and nerve cell loss in striatonigral and olivopontocerebellar structures. Epidemiological and clinical studies have reported potential involvement of autoimmune mechanisms in MSA pathogenesis. However, genetic etiology of this interaction remains unknown. We aimed to investigate genetic overlap between MSA and 7 autoimmune diseases and to identify shared genetic loci. METHODS: Genome-wide association study summary statistics of MSA and 7 autoimmune diseases were combined in cross-trait conjunctional false discovery rate analysis to explore overlapping genetic background. Expression of selected candidate genes was compared in transgenic MSA mice and wild-type mice. Genetic variability of candidate genes was further investigated using independent whole-exome genotyping data from large cohorts of MSA and autoimmune disease patients and healthy controls. RESULTS: We observed substantial polygenic overlap between MSA and inflammatory bowel disease and identified 3 shared genetic loci with leading variants upstream of the DENND1B and RSP04 genes, and in intron of the C7 gene. Further, the C7 gene showed significantly dysregulated expression in the degenerating midbrain of transgenic MSA mice compared with wild-type mice and had elevated burden of protein-coding variants in independent MSA and inflammatory bowel disease cohorts. CONCLUSION: Our study provides evidence of shared genetic etiology between MSA and inflammatory bowel disease with an important role of the C7 gene in both phenotypes, with the implication of immune and gut dysfunction in MSA pathophysiology. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Doenças Inflamatórias Intestinais , Atrofia de Múltiplos Sistemas , Animais , Estudo de Associação Genômica Ampla , Humanos , Doenças Inflamatórias Intestinais/genética , Camundongos , Camundongos Transgênicos , Atrofia de Múltiplos Sistemas/genética , alfa-Sinucleína/genética
18.
Metabolites ; 10(11)2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33212857

RESUMO

Metabolomics can be a tool to identify dietary biomarkers. However, reported food-metabolite associations have been inconsistent, and there is a need to explore further associations. Our aims were to confirm previously reported food-metabolite associations and to identify novel food-metabolite associations. We conducted a cross-sectional analysis of data from 849 participants (57% men) of the PopGen cohort. Dietary intake was obtained using FFQ and serum metabolites were profiled by an untargeted metabolomics approach. We conducted a systematic literature search to identify previously reported food-metabolite associations and analyzed these associations using linear regression. To identify potential novel food-metabolite associations, datasets were split into training and test datasets and linear regression models were fitted to the training datasets. Significant food-metabolite associations were evaluated in the test datasets. Models were adjusted for covariates. In the literature, we identified 82 food-metabolite associations. Of these, 44 associations were testable in our data and confirmed associations of coffee with 12 metabolites, of fish with five, of chocolate with two, of alcohol with four, and of butter, poultry and wine with one metabolite each. We did not identify novel food-metabolite associations; however, some associations were sex-specific. Potential use of some metabolites as biomarkers should consider sex differences in metabolism.

19.
J Am Heart Assoc ; 9(18): e015406, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896212

RESUMO

Background Offspring of parents with premature cardiovascular disease (CVD) have an increased risk of developing subclinical and clinical CVD. It is unclear whether this association differs by vascular beds in the offspring or by the age cut points used to define premature parental CVD. Methods and Results Using 3 generations of Framingham Heart Study participants, we assessed prevalent coronary artery calcification, the progression of coronary artery calcification over 6.1 years (median), carotid intima media thickness and the ankle-brachial index in 1046 offspring of parents with premature CVD before age 70 years, in 1618 offspring with both parents free of CVD and in 923 offspring with parents with CVD after age 70 years. We used different age cut points (55, 60, 65, and 70 years) to define premature parental CVD. In multivariable-adjusted models, offspring of parents with premature CVD (onset before age 65 years) displayed greater odds for prevalent coronary artery calcification (odds ratio [OR], 1.81; 95% CI, 1.35-2.43), higher carotid intima media thickness (OR, 1.50; 95% CI, 0.92-2.44) and lower ankle-brachial index (OR, 1.89; 95% CI, 1.00-3.58). These associations were generally consistent across different age cut points used to define premature parental CVD. The association with the progression of coronary artery calcification was less consistent. Conclusions Parental premature CVD is associated with increased subclinical CVD burden in the offspring, with consistent relations across different vascular beds and for different age cut points used to define premature parental CVD. Future studies should evaluate whether screening for subclinical CVD traits is warranted in offspring with premature parental CVD.


Assuntos
Doenças Assintomáticas/epidemiologia , Doenças Cardiovasculares/genética , Fatores Etários , Idoso , Índice Tornozelo-Braço , Doenças Cardiovasculares/epidemiologia , Espessura Intima-Media Carotídea , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Efeitos Psicossociais da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pais , Fatores de Risco , Calcificação Vascular/epidemiologia , Calcificação Vascular/genética
20.
Nutrients ; 12(8)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32824874

RESUMO

Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a community-based sample from Northern Germany (samples taken between 2010 and 2012). All participants (aged 25-82 years) underwent standardized examinations and completed a semi-quantitative food frequency questionnaire. Of several variables tested, the estimated glomerular filtration rate (eGFR) was statistically significantly (inversely) associated with lithium levels, mainly in individuals with slightly impaired renal function (eGFR < 75 mL/min/1.73 m2). Besides, lithium levels were positively associated with age and alcohol intake. Using reduced rank regression, we identified a dietary pattern explaining 8.63% variation in plasma lithium levels. Higher lithium levels were associated with higher intakes of potatoes, leafy vegetables, root vegetables, fruits, tea, beer, wine and dietetic products and lower intakes of pasta, rice, pork, chocolate, sweets, soft drinks, other alcoholic beverages, sauces and snacks. Our observations suggest that plasma lithium levels are associated inversely with kidney function, particularly in individuals with slightly impaired renal function, and positively with age and alcohol intake. Lithium at physiological levels was moderately related to an exploratory dietary pattern.


Assuntos
Consumo de Bebidas Alcoólicas , Dieta , Comportamento Alimentar/fisiologia , Alimentos , Fatores de Risco de Doenças Cardíacas , Rim/metabolismo , Lítio/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Estudos Transversais , Feminino , Alemanha , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Nefropatias/metabolismo , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
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