Decreased Plasma Level of TRIB3 is Associated with Circulating miR-124a in Patients with Type 2 Diabetes.

BACKGROUND: Recent evidence indicates that TRIB3 and miR-124 levels have been deregulated in type 2 diabetes (T2D); however, the simultaneous evaluation of these markers in diabetic patients has not been investigated to date. METHODS: This case-control study included 50 T2D patients and 40 age-gender matched controls. The circulation level of miR-124a was assessed by real-time PCR. TRIB3 plasma level was measured using the enzyme-linked im-munosorbent assay. RESULTS: Our findings revealed that the TRIB3 plasma level was significantly increased (p = 0.025), while miR-124a plasma levels were significantly reduced (p = 0.028) in diabetic patients compared to healthy subjects. ROC analysis showed that TRIB3 and miR-124a levels could discriminate control subjects and diabetic patients. Interestingly, a significant negative correlation was found between the TRIB3 and miR-124a plasma levels. Furthermore, there was a significant positive correlation between the TRIB3 plasma level with fasting blood glucose and insulin resistance. CONCLUSIONS: In this study, we showed deregulation of TRIB3 level in diabetic patients and its association with miR-124a circulating level and clinical parameters. These findings suggest that miR-124a may affect T2D incidence and progression by modulating the expression of TRIB3 protein level.

Co-expression profiling of plasma miRNAs and long noncoding RNAs in gastric cancer patients.

PURPOSE: The recent researches indicate that differential non-coding RNAs expression signatures could be associated with the pathogenesis of gastric cancer (GC). However, there are few studies focused on lncRNA-miRNAs co-expression profiling in GC patients. Therefore, in the present study the expression of H19 and MEG3 and their related miRNAs including miR-148a-3p, miR-181a-5p, miR-675-5p and miR-141-3p were determined in the plasma samples of GC patients and controls. MATERIALS AND METHODS: This case-control study included 62 GC patients and 40 age- sex matched controls. The non-coding RNA levels were assessed by real-time PCR. Further, using in silico analysis, we identified shared targets of studied miRNAs and performed GC-associated pathway enrichment analysis. RESULTS: Our results showed that the H19 level was significantly (P = 0.008) elevated and MEG3 expression was significantly (P = 0.002) down-regulated in GC patients compared to healthy participants. Furthermore, it was revealed that the miR-675-5p level was increased, while miR-141-3p plasma levels were significantly reduced in GC patients (P < 0.05). We did not observe a significant difference for miR-148a-3p (P = 0.682) and miR-181a-5p (P = 0.098) expression between groups. In addition, the expression levels of H19, MEG3 and miR-148a-3p were associated with some clinicopathological features of patients (P < 0.05). ROC analysis revealed that a combination of H19, MEG3 and miR-675-5p levels able to discriminate controls and GC subjects with 88.87% sensitivity and 85% specificity (AUC, 0.927; 0.85-0.96 CI, P < 0.0001). CONCLUSION: The results of current study demonstrated that combination of H19, MEG3 and miR-675-5p expression levels could provide a potential diagnostic panel for GC.

Genetic variants in long noncoding RNA H19 and MEG3 confer risk of type 2 diabetes in an Iranian population.

PURPOSE: Long-noncoding RNAs (lncRNAs) have been reported to regulate glucose homeostasis and insulin synthesis and secretion. However, the association of genetic variants of lncRNAs and type 2 diabetes (T2D) has not been evaluated. Therefore, in the present study we investigated the association between H19 rs217727 and H19 rs3741219 variants and MEG3 rs7158663 polymorphism with T2D susceptibility. MATERIALS AND METHODS: The study population consists of 969 subjects including 496 T2D patients and 473 non-diabetic age and sex-matched controls. The H19 and MEG3 variants genotyping were performed by PCR-RFLP method. RESULTS: Our results revealed that the T allele of rs217727 was more frequent in T2D group compared with controls (P = 0.007, OR = 1.1, 95% CI:1.02-1.18). Moreover, the rs217727-TT genotype was significantly associated with T2D after adjustment for age, BMI and lipid levels (P = 0.041, OR = 1.53, 95% CI: 1.01-2.32). However, no significant difference was detected for allele or genotype frequencies of H19 rs3741219 between T2D and controls (P = 0.71). Furthermore, the findings showed that the AA genotype of MEG3 rs7158663 was associated with significantly increased risks of T2D compared with the GG genotype (P = 0.026, OR = 1.79, 95% CI: 1.07-2.99). The results remained significance after analysis by logistic regression (P = 0.033, Adjusted OR = 1.72, 95% CI: 1.04-2.84). Finally, bioinformatics analysis showed that these SNPs could alter local RNA folding structure and also the miRNA-lncRNA interactions. CONCLUSIONS: Our findings provided the evidence of significant association between H19 rs217727-TT and MEG3 rs7158663-AA genotypes with T2D susceptibility.

Genetic Variants of Cytochrome b-245, Alpha Polypeptide Gene and Premature Acute Myocardial Infarction Risk in an Iranian Population.

BACKGROUND: Oxidative stress induced by superoxide anion plays critical roles in the pathogenesis of coronary artery disease (CAD) and hence acute myocardial infarction (AMI). The major source of superoxide production in vascular smooth muscle and endothelial cells is the NADPH oxidase complex. An essential component of this complex is p22phox, that is encoded by the cytochrome b-245, alpha polypeptide (CYBA) gene. The aim of this study was to investigate the association of CYBA variants (rs1049255 and rs4673) and premature acute myocardial infarction risk in an Iranian population. METHODS: The study population consisted of 158 patients under the age of 50 years, with a diagnosis of premature AMI, and 168 age-matched controls with normal coronary angiograms. Genotyping of the polymorphisms was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: There was no association between the genotypes and allele frequencies of rs4673 polymorphism and premature acute myocardial infarction (P>0.05). A significant statistical association was observed between the genotypes distribution of rs1049255 polymorphism and AMI risk (P=0.037). Furthermore, the distribution of AA+AG/GG genotypes was found to be statistically significant between the two groups (P=0.011). CONCLUSIONS: Our findings indicated that rs1049255 but not rs4673 polymorphism is associated with premature AMI.