RESUMEN
BACKGROUND: The p22phox gene encodes the main subunit of NADH/NADPH-oxidase. This enzyme is expressed in smooth muscle cells of arteries, and it produces the reactive oxygen species. On the other hand, oxidative stress plays a main role in the pathogenesis of coronary artery disease (CAD). AIM: The aim of this study is to evaluate the association between rs4673 and rs1049255 polymorphisms of p22phox gene with CAD in an Iranian population which was followed with a computational analysis approach. METHODS: In a cross-sectional study, we collected blood samples of 302 Iranian Caucasian including 143 patients and 159 healthy controls. Genotype of the polymorphisms was detected through PCR-RFLP method. A computational analysis was also performed using SNAP, Polyphen-2, Chou-Fasman, RNAsnp, and miRNA SNP databases. RESULTS: Data of case control study demonstrated that CT genotype (R = 1.84, 95% CI = 1.13-3.00, p = 0.014) and T allele (OR = 1.53, 95% CI = 1.09-2.15, p = 0.013) of rs4673 polymorphism, have a significant association with enhanced risk of CAD. But rs1049255 analysis demonstrated the absence of such an association with CAD. Indeed, in silico data analysis demonstrated that rs4673 transition could impact on function of p22phox protein (SNAP score 56, expected accuracy 75%; Polyphen-2 score 0.99, sensitivity 0.09, specificity 0.99). Data derived from miRNA SNP database demonstrated that rs1049255 polymorphism increases the affinity of attachment between has-miR-3689a-3b with 3'-UTR of p22phox gene. CONCLUSION: Our data demonstrated that rs4673 transition may be involved in susceptibility to CAD and could be applied as a potential biomarker for this disease.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , NADPH Oxidasas/genética , Anciano , Secuencia de Aminoácidos , Estudios de Casos y Controles , Biología Computacional/métodos , Enfermedad de la Arteria Coronaria/epidemiología , Estudios Transversales , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , NADPH Oxidasas/efectos adversos , Estrés Oxidativo , Polimorfismo Genético , Polimorfismo de Nucleótido SimpleRESUMEN
Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults in United States. Research indicates an association between oxidative stress and the development of diabetes complications. However, clinical trials with general antioxidants have failed to prove effective in diabetic patients. Mounting evidence from experimental studies that continue to elucidate the damaging effects of oxidative stress and inflammation in both vascular and neural retina suggest its critical role in the pathogenesis of DR. This review will outline the current management of DR as well as present potential experimental therapeutic interventions, focusing on molecules that link oxidative stress to inflammation to provide potential therapeutic targets for treatment or prevention of DR. Understanding the biochemical changes and the molecular events under diabetic conditions could provide new effective therapeutic tools to combat the disease.