Association of NFkB1 Gene Polymorphism with Inflammatory Markers in Patients of Type 2 Diabetes Mellitus with or without Renal Involvement in Eastern India

Aims: To evaluate the association of Nuclear factor kappa B1(NFkB1) gene polymorphism with inflammatory markers Urinary Monocyte Chemoattractant Protein 1 (UMCP1) and Tumor Necrosis Factor alfa (TNF alfa) in Patients of diabetes mellitus with or without renal involvement in Eastern India. Material and Methods: Consecutive Patients of Type 2 Diabetes Mellitus (DM) with or without microalbuminuria attending SCB MEDICAL COLLEGE and HOSPITAL Medical OPDs in between September 2018 to September 2019 were recruited in this study. Patients were subjected to blood and urine investigations. DNA extraction and Restriction fragment Length Polymorphism (RFLP) was done in Department of Biochemistry. Controls were unrelated healthy attendants with no history of Diabetes Mellitus, HTN, Chronic Kidney Disease (CKD). Results: Mean Systolic BP, Fasting Blood Glucose, Post Prandial Blood Glucose, HBA1c, Total Cholesterol were significantly higher in diabetes mellitus and diabetic nephropathy groups than control group. Estimated Glomerular Filtration Rate was significantly lower in diabetic nephropathy (p value < 0.001). UMCP1, Urinary Albumin Creatinine Ratio, TNF alfa were higher in diabetes mellitus and nephropathy with p value (<0.001, 0.006 < 0.001) respectively. In between DM and Diabetic Nephropathy groups nfkb1 gene expression, umcp1 and tnf alfa levels were significantly increased in Diabetic nephropathy with p value 0.019, <0.01, 0.001 respectively. Insertion/insertion NFkB1 gene polymorphisms were more in diabetic nephropathy group and were positively correlated with inflammatory markers UMCP1 (r = 0.517, p < 0.01) and TNF alfa (r = 0.172, p = 0.19). Conclusion: insertion/insertion NFkB1 gene polymorphism increases the risk of nephropathy by 2.52 times (OR = 2.52, 95% CI: 0.04 - 0.63, p value = 0.019) in diabetes patients in eastern India.

Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus:a cross-sectional cohort study

This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio(UACR)in patients with type 2 diabetes mellitus(T2DM)and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease(DKD).A total of 390 patients with T2DM were divided into three groups:normal albuminuria(UACR<30 mg/g,n=136,NA),microalbuminuria(UACR at 30-300 mg/g,n=132,MA),and clinical albuminuria(UACR>300 mg/g,n=122,CA).Circulating miR-154-5p,inflammatory(C-reactive protein(CRP);erythrocyte sedimentation rate(ESR);and tumor necrosis factor-a(TNF-α)and fibrotic markers(vascular endothelial growth factor(VEGF);transforming growth factor-β1(TGF-β1);and fibronectin(FN),and other biochemical indicators were assessed via real-time PCR,enzyme-linked immunosorbent assay,and chemiluminescence assay in patients with T2DM and 138 control subjects(NC).UACR,miR-154-5p,glycated hemoglobin(HbA1c),serum creatinine(sCr),blood urea nitrogen(BUN),ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were significantly higher and the estimated glomerular filtration rate(eGFR)was significantly lower in NA,MA,and CA groups than in NC subjects(P<0.05).Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c,sCr,BUN,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN and negatively correlated with eGFR(P<0.05).miR-154-5p,HbA1c,sCr,BUN,eGFR,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were important factors affecting UACR.These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.