RESUMEN
MicroRNA-499 (miR-499) rs3746444 polymorphism has been associated with the risk of coronary heart disease (CHD). However, results from several studies are inconsistent. This meta-analysis aimed to further investigate the possible association between miR-499 rs3746444 polymorphism and CHD risk. A total of 9 case-control studies included 5063 CHD cases and 4603 healthy subjects. The A allele at rs374644 was associated with significantly decreased CHD risk in the total population according to the allelic model (ORâ¯=â¯0.80, 95% CIâ¯=â¯0.68-0.93, Pâ¯=â¯0.005), homozygous model (ORâ¯=â¯0.52, 95% CIâ¯=â¯0.39-0.71, Pâ¯<â¯0.001) and heterozygous model (ORâ¯=â¯0.57, 95% CIâ¯=â¯0.43-0.77, Pâ¯<â¯0.001). A similar trend was found specifically in Asian and Chinese populations. In contrast, the wild-type GG genotype at rs374644 was associated with significantly increased CHD risk in the total population, according to the dominant model (ORâ¯=â¯1.83, 95% CIâ¯=â¯1.39-2.42, Pâ¯<â¯0.001), and a similar trend was found in Asian and Chinese populations. These results indicate that in the total population, as well as in Asian and Chinese populations, the wild-type GG genotype at rs374644 may be related to increased susceptibility to CHD, while the A allele may be protective against CHD.
Asunto(s)
Enfermedad Coronaria/genética , MicroARNs/genética , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , MicroARNs/metabolismo , Polimorfismo de Nucleótido Simple/genética , Factores de RiesgoRESUMEN
AIMS: Although therapeutic strategies for acute respiratory distress syndrome (ARDS) have achieved improvements, its mortality remains high. It has been reported that microRNAs (miRs) serve as therapeutic strategies for ARDS, while specific mechanisms of miR-494 remain poorly understood. Thus, the present study aimed to assess the effects of miR-494 on acute lung injury (ALI) in rat models of sepsis-associated ARDS and its regulatory mechanism. METHODS: Following establishment of sepsis-associated ARDS rat models, the ratio of wet to dry weight (W/D) in right lung tissues was detected. Moreover, the expression patterns of miR-494, NQO1 and Nrf2 were evaluated in left lung tissues of rats. The miR-494 was exogenously overexpressed in rats so as to analyze the effects of miR-494 on ALI, inflammatory response and oxidative stress. Meanwhile, the Nrf2 signaling pathway was activated in rats in order to show the regulatory mechanism of miR-494 in ALI. And the target gene of miR-494 was identified by dual-luciferase reporter assay. KEY FINDINGS: The findings firstly revealed upregulated miR-494, and enhanced inflammatory response, oxidative stress and ALI in rat models of sepsis-associated ARDS. Additionally, MiR-494 negatively regulated NQO1 and blocked the Nrf2 signaling pathway. Moreover, ectopic expression of miR-494 promoted inflammatory response, oxidative stress and ALI. However, the activation of Nrf2 signaling pathway reversed these effects of miR-494. SIGNIFICANCE: Our key findings highlight the value of miR-494 inhibition as a therapeutic target for sepsis-associated ARDS, as a result of miR-494 accelerated ALI in rats with sepsis-associated ARDS through NQO1-mediated inactivation of Nrf2 signaling pathway.