RESUMEN
Recent studies have indicated that microRNA and VEGF are considered to be genetic modifiers and are associated with elevated levels of fetal haemoglobin HbF, and thus they reduce the clinical impact of sickle haemoglobin (HbS) patients. This cross-sectional study was performed on clinical confirmed subjects of SCD cases. miR-423-rs6505162 C>T and VEGF-2578 C>A genotyping was conducted by ARMS-PCR in SCD and healthy controls. A strong clinical significance was reported while comparing the association of miR-423 C>T genotypes between SCD patients and controls (p = 0.031). The microRNA-423 AA genotype was associated with an increased severity of SCD in codominant model with odd ratio (OR = 2.36, 95% CI, (1.15-4.84), p = 0.018) and similarly a significant association was observed in recessive inheritance model for microRNA-423 AA vs (CC+CA) genotypes (OR = 2.19, 95% CI, (1.32-3.62), p < 0.002). The A allele was associated with SCD severity (OR = 1.57, 95% CI, (1.13-2.19), p < 0.007). The distribution of VEGF-2578 C>A genotypes between SCD patients and healthy controls was significant (p < 0.013). Our results indicated that in the codominant model, the VEGF-2578-CA genotype was strongly associated with increased SCD severity with OR = 2.56, 95% CI, (1.36-4.82), p < 0.003. The higher expression of HbA1 (65.9%), HbA2 (4.40%), was reported in SCD patients carrying miR-423-AA genotype than miR-423 CA genotype in SCD patients carrying miR-423 CA genotype HbA1 (59.98%), HbA2 (3.74%) whereas SCD patients carrying miR-423 CA genotype has higher expression of HbF (0.98%) and HbS (38.1%) than in the patients carrying AA genotype HbF (0.60%), HbS (36.1%). ARMS-PCR has been proven to be rapid, inexpensive and is highly applicable to gene mutation screening in laboratories and clinical practices. This research highlights the significance of elucidating genetic determinants that play roles in the amelioration of the HbF levels that is used as an indicator of severity of clinical complications of the monogenic disease. Further well-designed studies with larger sample sizes are necessary to confirm our findings.
RESUMEN
Vascular endothelial dysfunction is caused by dyslipidemia, hypertension, and deficiency of antioxidant systems. In this study, the protective effect of a flavonol, morin was investigated in high-fat diet (HFD)-induced dyslipidemia and vascular endothelium dysfunction. The dose-dependent attenuating effect of morin was tested at doses of 50 and 100 mg/kg/day in an in-vivo model of HFD-induced dyslipidemia using rats whereas vascular endothelial reactivity was assessed in isolated rat aorta using ex-vivo organ bath setup. Morin administration in HFD-induced dyslipidemic rats for three weeks, resulted in a significant decrease in the body weight, LW/BW ratio as compared to rats treated with HFD only where the increase in body weight was observed. Significant reduction in the waist, BMI and lee index was also observed after morin treatment in HFD-induced dyslipidemic rats. In the lipid profile studies, HFD group showed a significant increase in the total cholesterol, triglyceride, LDL, and VLDL levels while HDL levels were decreased significantly, whereas morin treatment reversed all these parameters which were comparable to standard diet (SD) group. In the ex-vivo isolated aorta studies, HFD-induced endothelium dysfunction was observed, whereas it was reversed in the aorta of animals treated with morin at doses of 50 and 100 mg/kg/day, comparable to SD group. Morin treatment produced dose-dependent improvement in lipid profile and vascular endothelium protection, thus rationalizing its medicinal use in dyslipidemia and cardiovascular-related endothelial disorders.