High serum miR-421 is associated with metabolic dysregulation and inflammation in patients with metabolic syndrome.

Aim: To explore the association of circulating miRNAs with adiposity, metabolic status and inflammatory biomarkers in patients with metabolic syndrome (MetS). Methods: Serum levels of 372 miRNAs were measured in patients with (n = 6) and without MetS (n = 6) by quantitative PCR array, and dysregulated miRNAs were validated in a larger cohort (MetS, n = 89; non-MetS, n = 144). Results: In the screening study, seven miRNAs were dysregulated in patients with MetS, and miR-421 remained increased in the validation study. miR-421 was associated with a high risk of MetS and insulin resistance and hypertension and correlated with glycated hemoglobin, triacylglycerols, high-sensitivity CRP, IL-6, resistin and adiponectin (p < 0.05). Conclusion: Circulating miR-421 is a potential biomarker for insulin resistance, metabolic dysregulation and inflammatory status in patients with MetS.

High serum miR-421 is associated with metabolic dysregulation and inflammation in patients with metabolic syndrome

ABSTRACT: To explore the association of circulating miRNAs with adiposity, metabolic status and inflammatory biomarkers in patients with metabolic syndrome (MetS). METHODS: Serum levels of 372 miRNAs were measured in patients with (n = 6) and without MetS (n = 6) by quantitative PCR array, and dysregulated miRNAs were validated in a larger cohort (MetS, n = 89; non-MetS, n = 144). RESULTS: In the screening study, seven miRNAs were dysregulated in patients with MetS, and miR-421 remained increased in the validation study. miR-421 was associated with a high risk of MetS and insulin resistance and hypertension and correlated with glycated hemoglobin, triacylglycerols, high-sensitivity CRP, IL-6, resistin and adiponectin (p < 0.05). CONCLUSION: Circulating miR-421 is a potential biomarker for insulin resistance, metabolic dysregulation and inflammatory status in patients with MetS.

Polymorphisms in genes encoding metalloproteinase 9 and Lymphotoxin-Alpha can influence warfarin treatment

Objectives: Warfarin treatment is influenced by environmental and genetic factors. The influence of polymorphisms in genesencoding metalloproteinase 9 (MMP9), lymphotoxin-alpha (LTA) andTNFSF14 (LIGHT), related to the inflammatory process ofcoronary artery disease, on warfarin dose and time to reach target was investigated in this study.Methods: Outpatients on warfarin treatment (n=227), 20 to 92 years, were enrolled at the Institute Dante Pazzanese of Cardiology(IDPC). Genomic DNA was obtained from peripheral whole blood to evaluate MMP9 rs17576 (Gln279Arg, A>G), LTA rs1041981(Thr60Asn, C>A) and rs909253 (c.252T>C) and TNFSF14rs2291668 (c.147C>T) and rs344560 (Lys214Glu, G>A) polymorphismsby pyrosequencing in Q24PyroMark.Results: The patients carrying MMP9 rs17576GG genotype were more likely to require a lower warfarin weekly dose (OR:2.73, 95% CI: 1.01-7.41, p=0.048). Also, LTA rs909253 variant was associated with a longer time to reach the target internationalnormalized ratio (INR) (OR: 1.98, 95% CI: 1.02-3.86, p=0.043). Age was inversely correlated with the target INR (r=-0.387, p<0.001),and dose was directly correlated with time to reach target INR (r=0.244, p<0.001).Conclusion: MMP9 rs17576 variant may have an important influence on warfarin weekly dose, and that LTA rs909253polymorphism may also influence the time to reach the target INR.