RESUMO
Numerous studies have evaluated the association between Arg389Gly polymorphism in the ß1 adrenergic receptor gene and heart failure risk. However, the specific association is still controversial. We performed a meta-analysis of all case-control studies that evaluated the association between Arg389Gly polymorphism and heart failure in humans. Studies were identified in the PubMed, Embase, and China National Knowledge Infrastructure databases. Two reviewers independently assessed the studies. Six case-control studies with a total of 1736 participants were included in the meta-analysis, including 882 cases with heart failure and 854 controls, and our results showed no association between the Arg389Gly polymorphism and heart failure [ArgArg vs GlyGly: odds ratio (OR) = 0.84, 95% confidence interval (CI) 0.59-1.20; ArgArg vs ArgGly: OR = 0.95, 95%CI 0.78-1.16; dominant model: OR = 1.08, 95%CI 0.89-1.31; recessive model: OR = 0.96, 95%CI 0.69-1.35]. No publication bias was found in the present study (all P values > 0.05). In conclusion, the ß1 adrenergic receptor gene Arg389Gly polymorphism might not be associated with heart failure risk. Further large and well-designed studies are needed to confirm this conclusion.
Assuntos
Predisposição Genética para Doença , Insuficiência Cardíaca/genética , Hipertensão/genética , Receptores Adrenérgicos beta 1/genética , China , Feminino , Estudos de Associação Genética , Insuficiência Cardíaca/patologia , Humanos , Hipertensão/patologia , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
It has been suggested that the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is linked to susceptibility to myocardial infarction (MI). In this study, we performed a meta-analysis to assess the relationship between ACE I/D polymorphism and MI in the Chinese Han population. Eight studies including a total of 1609 subjects were selected for inclusion in the analysis. The references were retrieved using the PubMed and China National Knowledge Infrastructure databases. The analyses were performed using the STATA 12.0 software. ORs and 95%CI were assessed after the collected data were pooled for analysis. There was a significant association between ACE I/D polymorphism and MI in the Chinese Han population (II vs DD: OR = 0.40, 95%CI = 0.31-0.53; II vs DI: OR = 0.72, 95%CI = 0.57-0.91; the dominant model: OR = 1.74, 95%CI = 1.41-2.16; the recessive model: OR = 0.47, 95%CI = 0.38-0.60). The sensitivity analysis further confirmed the result. Publication bias was not observed in this meta-analysis. The ACE I/D polymorphism may be a risk factor for MI in the Chinese Han population. However, larger studies with a stratified case-control population and biological characterization are needed to validate this finding.
Assuntos
Povo Asiático/genética , Etnicidade/genética , Predisposição Genética para Doença , Mutação INDEL/genética , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Peptidil Dipeptidase A/genética , Intervalos de Confiança , Humanos , Razão de Chances , Viés de Publicação , Fatores de RiscoRESUMO
The proposed role of Niemann-Pick type C1 protein (NPC1) in the delivery of low-density lipoprotein (LDL) cholesterol to the sterol regulatory element binding protein (SREBP):SREBP cleavage activation protein (SCAP) complex in the endoplasmic reticulum has been largely based on indirect studies and remains contentious. The major aim of the present study was to assess whether NPC1 is involved in the delivery of LDL cholesterol to the SREBP:SCAP complex. A cell line stably expressing green fluorescence protein-SCAP was cultured in the presence of U18666A, which can induce a Niemann-Pick type C disease phenotype, in order to locate the SREBP:SCAP complex by fluorescence microscopy. Our major finding was that defective NPC1 caused a delay in the ability of LDL cholesterol to suppress SREBP processing. This was shown in a time-course experiment by the effect of LDL on green fluorescence protein-SCAP movement when cells were treated with pharmacological agents to induce a Niemann-Pick type C disease phenotype. We demonstrated directly by fluorescence microscopy that defective NPC1 causes a delay in LDL cholesterol delivery to the endoplasmic reticulum where SCAP senses cholesterol.
Assuntos
Animais , Proteínas de Transporte/fisiologia , LDL-Colesterol/metabolismo , Retículo Endoplasmático/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Glicoproteínas de Membrana/fisiologia , Proteínas de Membrana/metabolismo , Doenças de Niemann-Pick/etiologia , Linhagem Celular , Microscopia de Fluorescência , Doenças de Niemann-Pick/metabolismo , FenótipoRESUMO
The proposed role of Niemann-Pick type C1 protein (NPC1) in the delivery of low-density lipoprotein (LDL) cholesterol to the sterol regulatory element binding protein (SREBP):SREBP cleavage activation protein (SCAP) complex in the endoplasmic reticulum has been largely based on indirect studies and remains contentious. The major aim of the present study was to assess whether NPC1 is involved in the delivery of LDL cholesterol to the SREBP:SCAP complex. A cell line stably expressing green fluorescence protein-SCAP was cultured in the presence of U18666A, which can induce a Niemann-Pick type C disease phenotype, in order to locate the SREBP:SCAP complex by fluorescence microscopy. Our major finding was that defective NPC1 caused a delay in the ability of LDL cholesterol to suppress SREBP processing. This was shown in a time-course experiment by the effect of LDL on green fluorescence protein-SCAP movement when cells were treated with pharmacological agents to induce a Niemann-Pick type C disease phenotype. We demonstrated directly by fluorescence microscopy that defective NPC1 causes a delay in LDL cholesterol delivery to the endoplasmic reticulum where SCAP senses cholesterol.