ABSTRACT
BACKGROUND: Reactive oxygen species are thought to contribute to the development of renal damage. The P22phox subunit of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase, encoded by the cytochrome b245a polypeptide gene, CYBA, plays a key role in superoxide anion production. We investigated the association of CYBA rs7195830 polymorphism with estimated glomerular filtration rate (eGFR) and the role it plays in the pathogenesis of chronic kidney disease (CKD) in a Han Chinese sample. METHODS: The Gaoyou study enrolled 4473 participants. Serum levels of creatinine were measured and eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equations. The CYBA polymorphisms were genotyped. Then we investigated the association between eGFR and the rs7195830 polymorphism in the recessive model. RESULTS: The AA genotype of rs7195830 was associated with significantly lower values of eGFR compared with the GG and AG genotypes ((102.76 ± 17.07) ml×min(-1)×1.73 m(-2) vs. (105.08 ± 16.30) ml×min(-1)± 1.73 m(-2)). The association remained significant in the recessive model after adjusting for age, gender, body mass index, smoking, hypertension, diabetes mellitus, uric acid, triglyceride, low density lipoprotein cholesterol and high density lipoprotein cholesterol (ß=1.666, P=0.031). The rs7195832 AA genotype was an independent risk factor for CKD: eGFR <60 ml×min(-1)×1.73 m(-2) (odds ratio=3.32; 95% CI=1.21-9.13). CONCLUSION: The AA genotype of rs7195830 is independently associated with lower estimated glomerular filtration rate and is significantly associated with CKD.
Subject(s)
Glomerular Filtration Rate/genetics , NADPH Oxidases/genetics , Polymorphism, Genetic/genetics , Adolescent , Adult , Aged , Asian People/genetics , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/genetics , Young AdultABSTRACT
BACKGROUND: Previous studies demonstrated dysregulated expression of microRNAs (miRNAs) in the myocardium of patients with dilated cardiomyopathy (DCM). This study investigated levels of miRNAs in the circulation of DCM patients, and the value of miRNAs as biomarkers for DCM. METHODS AND MATERIALS: In 45 DCM patients and 39 age- and sex-matched controls, circulating miR-423-5p, miR-126, miR-361-5p, miR-155, and miR-146a concentrations were measured and correlated to cardiac functional parameters, including left ventricular ejection fraction (LVEF) and N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: Plasma levels of miR-126 and miR-361-5P did not differ between the DCM and control groups (p = 0.331 and p = 0.784, respectively). Plasma levels of the immunity-associated miRNAs, miR-146a and miR-155, did not differ between the DCM and control groups (p = 0.437 and p = 0.702, respectively). Levels of circulating miR-423-5p were significantly greater in the DCM group (p = 0.003). Further, there was a positive correlation between plasma levels of miR-423-5p and NT-proBNP (r = 0.430, p = 0.003). MiR-423-5p distinguished DCM cases from controls with an area under the curve (AUC) receiver operating characteristic (ROC) curve of 0.674 (95% CI, 0.555-0.793). CONCLUSIONS: Patients with DCM have elevated plasma miR-423-5p levels. The plasma concentration of miR-423-5p was positively correlated with the level of NT-proBNP. Circulating levels of miR-423-5p could be served as a diagnostic biomarker for heart failure caused by DCM. Plasma levels of immunity-associated miR-146a, -155, and -126 were not significantly different between DCM and control groups.
