RESUMO
Recently, several studies reported the association between miR-146a rs2910164 polymorphism and coronary artery disease (CAD) risk. However, the results were inconclusive. We therefore did a meta-analysis to investigate this association. Electronic databases, including PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) databases, were searched. The strength of association was assessed by calculating odds ratios (OR) and 95% confidence interval (CI). Five eligible studies included in this meta-analysis. The total sample size of this meta-analysis was 1565 cases and 1541 controls. We found that miR-146a rs2910164 polymorphism was significantly associated with an increased CAD risk (OR = 1.19; 95% CI 1.07 - 1.32; P = 0.002). In the subgroup analysis by race, miR-146a rs2910164 polymorphism was significantly associated with an increased CAD risk in Asians (OR = 1.18; 95% CI 1.04 - 1.33; P = 0.008). However, we did not find significant result in Caucasians (OR = 1.22; 95% CI 0.86 - 1.74; P = 0.25). In the subgroup analysis by age, we found that miR-146a rs2910164 polymorphism increased CAD risk in old population (OR = 1.22; 95% CI 1.09 - 1.38; P = 0.0008). In conclusion, this meta-analysis found that miR-146a rs2910164 polymorphism was significantly associated with CAD risk.
Assuntos
Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Fatores Etários , Povo Asiático , Estudos de Casos e Controles , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Razão de Chances , Fatores de Risco , População BrancaRESUMO
It is accepted that amyloid ß-derived diffusible ligands (ADDLs) have a prominent role in triggering the early cognitive deficits that constitute Alzheimer's disease (AD). However, there is still no effective treatment for preventing or reversing the progression of the disease. Targeting α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor trafficking and its regulation is a new strategy for AD early treatment. Here we investigate the effect and mechanism of L-Stepholidine (L-SPD), which elicits dopamine D1-type receptor agonistic activity, while acting as D2-type receptor antagonist on cognition and synaptic plasticity in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice, and hippocampal cultures or slices treated with ADDLs. L-SPD could improve the hippocampus-dependent memory, surface expression of glutamate receptor A (GluA1)-containing AMPA receptors and spine density in hippocampus of APP/PS1 transgenic mice. L-SPD not only rescued decreased phosphorylation and surface expression of GluA1 in hippocampal cultures but also protected the long-term potentiation in hippocampal slices induced by ADDLs. Protein kinase A (PKA) agonist Sp-cAMPS or D1-type receptor agonist SKF81297 had similar effects, whereas PKA antagonist Rp-cAMPS or D1-type receptor antagonist SCH23390 abolished the effect of L-SPD on GluA1 trafficking. This was mediated mainly by PKA, which could phosphorylate serine residue at 845 of the GluA1. L-SPD may be explored as a potential therapeutic drug for AD through a mechanism that improves AMPA receptor trafficking and synaptic plasticity via activating D1/PKA signaling pathway.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Antipsicóticos/farmacologia , Berberina/análogos & derivados , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Transtornos da Memória/tratamento farmacológico , Receptores de Dopamina D1/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Berberina/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/genética , Agonistas de Dopamina/farmacologia , Masculino , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Camundongos , Camundongos Transgênicos , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/genética , Transdução de SinaisRESUMO
BACKGROUND: Increasing evidence suggests an association between elevated serum aminotransferase levels and metabolic disorders (metabolic syndrome, hyperlipemia and diabetes mellitus). However, the significance of relatively low levels of aminotransferases in relation to metabolic disorders has not been fully investigated in the general population. We investigated the association between serum amiontransferase levels and metabolic disorders using data from a survey in Jilin province, China. METHODS: In 2007, a survey was conducted throughout Jilin, China, covering both urban and rural areas. A total of 3835 people, 18 to 79 years old including 1761 men and 2074 women, underwent real-time ultrasonography, blood tests including aspartate aminotransferase and alanine aminotransferase, and had interviews with a structured questionnaire. RESULTS: Serum aminotransferase levels within the normal range were associated with metabolic syndrome independent of age, occupation, cultural and educational level, income, body mass index, waist circumference, smoking, and alcohol intake. Compared with the lowest level (<20 IU/L), the adjusted odds ratios for ALT levels of 20-29, 30-39, 40-49 and >50 IU/L were 1.92, 2.50, 2.97, and 3.52 in men, and 1.38, 1.54, 3.06, and 2.62 in women, respectively. Near-normal serum aminotransferase levels associated with hyperlipemia, NAFLD, DM were also found in the study. CONCLUSIONS: Normal to near-normal serum aminotransferase levels are associated with metabolic disorders. Serum ALT levels of 21-25 IU/L for men, and 17-22 IU/L for women are suggested as cutoff levels that detect metabolic disorders affecting the liver.
