Association of NFkB1 Gene Polymorphism with Inflammatory Markers in Patients of Type 2 Diabetes Mellitus with or without Renal Involvement in Eastern India
Department of Medicine, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, India
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Department of Biochemistry, Laboratory of Molecular Science, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, India
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Department of Biochemistry, Laboratory of Molecular Science, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, India
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Department of Medicine, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, India
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Department of Medicine, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, India
1 Department of Medicine, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, India
2 Department of Biochemistry, Laboratory of Molecular Science, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, India
3 Department of Biochemistry, Laboratory of Molecular Science, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, India
4 Department of Medicine, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, India
5 Department of Medicine, Sriram Chandra Bhanja Medical College, Cuttack, Odisha, 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.
IDF (2017) IDF Diabetes Atlas 2017. 8th Edition, Country Report from India. http://diabetesatlas.org/resources/2017-atlas.html
Wolf, G.F., et al. (2007) Cellular & Molecular Mechanisms of Proteinuria in Diabetic Nephropathy. Nephron Physiology, 106, 26-31. https://doi.org/10.1159/000101797
Behera, S.R., et al. (2017) Morbidity Profile and Causes of Mortality in Type 2 Diabetes Patients: Data from a Tertiary Teaching Hospital from Eastern India. Journal of Diabetes Mellitus, 7, 195-211. https://doi.org/10.4236/jdm.2017.73016
Chawla, R. (2012) Complications of Diabetes. Jaypee Brothers Medical Publishers, New Delhi, 1-53. https://doi.org/10.5005/jp/books/11685
Agarwal, R.P., Ola, V. and Bishnoi, P. (2014) Prevalence of Micro and Macrovascular Complications and Their Risk Factors in Type-2 Diabetes Mellitus. The Journal of the Association of Physicians of India, 62, 504-508.
Pradeepa, R., Prabhu, A.K. and Jebarani, S. (2011) Use of Large Diabetes Electronic Medical Record System in India: Clinical and Research Applications. Journal of Diabetes Science and Technology, 5, 543-552. https://doi.org/10.1177/193229681100500309
Varghese, A., Deepa, R. and Reema, M. (2001) Prevalence of Microalbuminuria in Type-2 Diabetes Mellitus at a Diabetes Centre in South India. Postgraduate Medical Journal, 77, 399-402. https://doi.org/10.1136/pmj.77.908.399
Yajnik, C.S., Naik, S.S. and Rout, K.N. (1992) Urinary Albumin Excretion Ratio (AER) in Newly Diagnosed Type 2 Indian Diabetic Patients Is Associated with Central Obesity and Hyperglycemia. Diabetes Research and Clinical Practice, 17, 55-60. https://doi.org/10.1016/0168-8227(92)90044-R
Diabetes Drafting Group (1985) Prevalence of Small Vessel and Large Vessel Disease in Diabetic Patients from 14-Centres. The World Health Organisation Multinational Study of Vascular Disease in Diabetics. Diabetologia, 28, 615-640. https://doi.org/10.1007/BF00290267
Das, S., Mishra, R.K. and Jena, B.B. (1991) Mortality Events amongst NIDDM Patients in Orissa. Journal of the Association of Physicians of India, 39, 519-520.
Rajapurkar, M.M., John, G.T., Kirpalini, A.L., Abraham, G., Agarwal, S.K., Almeida, A.F., Gang, S., Gupta, A., Modi, G., Pahari, D., Pisharody, R., Prakash, J., Raman, A., Rana, D.S., Sharma, R.K., Sahoo, R.N., Sakhuja, V., Tatapudi, R.R. and Jha, V. (2012) What Do We Know about Chronic Kidney Disease in India; First Report of the Indian CKD Registry. BMC Nephrology, 13, 10. https://doi.org/10.1186/1471-2369-13-10
Association of NFkB1 Gene Polymorphism with Inflammatory Markers in Patients of Type 2 Diabetes Mellitus with or without Renal Involvement in Eastern India — Oak Academic Publishing
Das, S., Chandrakanth, M.V., Rout, S.B., Mohanty, R., Singh, S.C., Pattnaik, M. and Sethy, B. (2012) Study of Markers of Atherosclerosis Including Insulin Resistance in Patients with Chronic Renal Failure. Journal of Diabetes Mellitus, 2, 208-213. https://doi.org/10.4236/jdm.2012.22033
Unnikrishnan, R., Rema, M., Pradeepa, R., Deepa, M., Shanthirani, S., Deepa, R. and Mohan, V. (2007) Prevalence and Risk Factors of Diabetic Nephropathy in an Urban South Indian Population, the Chennai Urban Rural Epidemiology Study (CURES 45). Diabetes Care, 30, 2019-2024. https://doi.org/10.2337/dc06-2554
Mani, M.K. (1998) Patterns of Renalp Disease in Indigenous Populations in India. Nephrology, 4, S4-S7. https://doi.org/10.1111/j.1440-1797.1998.tb00461.x
Nayak, S., et al. (2017) Evaluation of Type of Nephropathy in Patients of Type-2 Diabetes Mellitus Department of Medicine, SCB Medical College, Cuttack, India. Journal of Diabetes Mellitus, 7, 281-293. https://doi.org/10.4236/jdm.2017.74023
Esposito, K., Nappo, F., Marfella, R., Giugliano, G., Giugliano, F., Ciotola, M., Quagliaro, L., Ceriello, A. and Giugliano, D. (2002) Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress. Circulation, 106, 2067-2072. https://doi.org/10.1161/01.CIR.0000034509.14906.AE
Karin, M. and Ben-Neriah, Y. (2000) Phosphorylation Meets Ubiquitination: The Control of NF-[kappa]B Activity. Annual Review of Immunology, 18, 621-663. https://doi.org/10.1146/annurev.immunol.18.1.621
Barnes, P.J. and Karin, M. (1993) Nuclear Factor-kappaB: A Pivotaltrans-Cription Factor in Chronic Inflammatory Diseases. The New England Journal of Medicine, 36, 1066-1071. https://doi.org/10.1056/NEJM199704103361506
Yang, X., Li, P., Tao, J., Qin, C., Cao, Q., Gu, J., Deng, X., Wang, J., Liu, X., Wang, Z., Wu, B., Gu, M., Lu, Q. and Yin, C. (2014) Association between NFKB1-94ins/del ATTG Promoter Polymorphism and Cancer Susceptibility: An Updated Meta-Analysis. International Journal of Genomics, 2014, Article ID: 612972. https://doi.org/10.1155/2014/612972
Das, S. and Misra, D.P. (2012) Prevalence of Inflammatory Markers (High-Sensitivity C-Reactive Protein, Nuclear Factor-kB, and Adiponectin) in Indian Patients with Type 2 Diabetes Mellitus with and without Macrovascular Complications. Metabolic Syndrome and Related Disorders, 10, 209-213. https://doi.org/10.1089/met.2011.0044
Gautam, A., Gupta, S., et al. (2013) Association of Biomarkers of Inflammation and Oxidative Stress with the Risk of Chronic Kidney Disease in Type 2 Diabetes Mellitus in North Indian Population. Journal of Diabetic Complications, 27, 548-552. https://doi.org/10.1016/j.jdiacomp.2013.07.005
Tilak, P., et al. (2008) MCP-1/CCL2: A New Diagnostic Marker and Therapeutic Target for Progressive Renal Injury in Diabetic Nephropathy. American Journal of Physiology-Renal Physiology, 294, F697-F701. https://doi.org/10.1152/ajprenal.00016.2008
National Kidney Foundation (2012) KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. American Journal of Kidney Diseases, 60, 850-886.
World Health Organization (2015) Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus. World Health Organization, Geneva.
Senol Tuncay, S., Okyay, P. and Bardakci, F. (2010) Identification of NFkappaB1 and NF-kappaBIAlpha Polymorphisms Using PCR-RFLP Assay in a Turkish Population. Biochemical Genetics, 48, 104-112. https://doi.org/10.1007/s10528-009-9302-y
Ziyadeh, G. and Wolf, F.N. (2008) Pathogenesis of the Podocytopathy and Proteinuria in Diabetic Glomerulopathy. Current Diabetes Reviews, 4, 39-45. https://doi.org/10.2174/157339908783502370
Palazhy, S., et al. (2017) Lipid Abnormalities in Diabetic Nephropathy. Diabetes & Metabolism Journal, 41, 128-134. http://e-dmj.org https://doi.org/10.4093/dmj.2017.41.2.128
Viberti, G. and Wheeldon, N.M. (2002) Microalbuminuria Reduction with Valsartan in Patients with Type 2 Diabetes Mellitus: A Blood Pressure-Independent Effect. Circulation, 106, 672-678. https://doi.org/10.1161/01.CIR.0000024416.33113.0A
Thompson, W.L. and Van Eldik, L.J. (2009) Inflammatory Cytokines Stimulate the Chemokines CCL2/MCP-1 and CCL7/MCP-3 through NFkB and MAPK Dependent Pathways in Rat Astrocytes [Corrected]. Brain Research, 1287, 47-57. https://doi.org/10.1016/j.brainres.2009.06.081
Wang, Y., Chen, J., Chen, L., et al. (1997) Induction of Monocyte Chemoattractant Protein-1 in Proximal Tubule Cells by Urinary Protein. Journal of the American Society of Nephrology, 8, 1537-1545.
Gupta, S., Kalra, S., Mehndiratta, M., Kalra, O.P., Shukla, R. and Gambhir, J.K. (2015) Association of Tumor Necrosis Factor (TNF) Promoter Polymorphisms with Plasma TNF-α Levels and Susceptibility to Diabetic Nephropathy in North Indian Population. Journal of Diabetes and Its Complications, 29, 338-342. https://doi.org/10.1016/j.jdiacomp.2015.01.002
Zhou, B., Qie, M., Wang, Y., Yan, L., Zhang, Z., Liang, A., Wang, T., Wang, X., Song, Y. and Zhang, L. (2010) Relationship between NFKB1-94 Insertion/Deletion ATTG Polymorphism and Susceptibility of Cervical Squamous Cell Carcinoma Risk. Annals of Oncology, 21, 506-511. https://doi.org/10.1093/annonc/mdp507
Kalra, O.P., et al. (2017) Genetic Basis of Diabetic Nephropathy. Annals of the National Academy of Medical Sciences (India), 53, 1-20. https://doi.org/10.1055/s-0040-1712740