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Current Diabetes Reviews

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ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

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Research Article

The Possible Association of IL-6R Gene Polymorphisms in the Development of Diabetic Nephropathy

Author(s): Ebrahim Ebrat, Seyyedeh Mina Hejazian, Elham Ahmadian, Sepideh Zununi Vahed, Majid Mobasseri and Mohammadreza Ardalan*

Volume 20, Issue 8, 2024

Published on: 17 October, 2023

Article ID: e171023222283 Pages: 5

DOI: 10.2174/0115733998245369231009111221

Price: $65

Abstract

Background: Diabetic nephropathy (DN) is a common complication of type 2 diabetes (T2D). Chronic inflammation and a combination of environmental and genetic factors are involved in the pathogenesis and development of DN.

Objective: This case-control study aimed to determine the relationship between rs7529229 and rs2228145 polymorphisms of the IL-6R gene with the incidence of nephropathy among T2D patients.

Methods: Fifty-six diabetic patients with nephropathy and 57 T2D patients without nephropathy were included based on inclusion criteria, along with 150 healthy individuals.

Results: The frequencies of AC and CC genotype distributions of the rs2228145 polymorphism in DN patients were significantly higher than in healthy individuals (24.1 and 9.3% versus 10.7 and 6.7%, respectively, P= 0.02). Moreover, the frequency of allele C was higher in DN patients compared to healthy controls (21.30% versus 12%, P=0.025). However, genotype distribution and allele frequencies of the rs7529229 IL-6R polymorphism in DN patients were not statistically significant in comparison with diabetic patients and healthy individuals (P> 0.05).

Conclusion: The results showed that the allele and genotype distribution frequencies of rs2228145 IL-6R gene polymorphism in patients with DN were significantly higher than in healthy individuals. Therefore, the presence of this polymorphism may be involved in the development of diabetic nephropathy in this population.

[1]
Oltean S, Qiu Y, Ferguson JK, et al. Vascular endothelial growth factor-a165b is protective and restores endothelial glycocalyx in diabetic nephropathy. J Am Soc Nephrol 2015; 26(8): 1889-904.
[http://dx.doi.org/10.1681/ASN.2014040350] [PMID: 25542969]
[2]
Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci 2013; 124(3): 139-52.
[http://dx.doi.org/10.1042/CS20120198] [PMID: 23075333]
[3]
Satirapoj B, Adler SG. Prevalence and management of diabetic nephropathy in western countries. Kidney Dis 2015; 1(1): 61-70.
[http://dx.doi.org/10.1159/000382028] [PMID: 27536666]
[4]
Feigerlová E, Battaglia-Hsu SF. IL-6 signaling in diabetic nephropathy: From pathophysiology to therapeutic perspectives. Cytokine Growth Factor Rev 2017; 37: 57-65.
[http://dx.doi.org/10.1016/j.cytogfr.2017.03.003] [PMID: 28363692]
[5]
Su H, Lei CT, Zhang C. Interleukin-6 signaling pathway and its role in kidney disease: An update. Front Immunol 2017; 8: 405.
[http://dx.doi.org/10.3389/fimmu.2017.00405] [PMID: 28484449]
[6]
Wang H, Zhang Z, Chu W, Hale T, Cooper JJ, Elbein SC. Molecular screening and association analyses of the interleukin 6 receptor gene variants with type 2 diabetes, diabetic nephropathy, and insulin sensitivity. J Clin Endocrinol Metab 2005; 90(2): 1123-9.
[http://dx.doi.org/10.1210/jc.2004-1606] [PMID: 15562008]
[7]
Dalla Vestra M, Mussap M, Gallina P, et al. Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. J Am Soc Nephrol 2005; 16(S1): S78-82.
[http://dx.doi.org/10.1681/ASN.2004110961] [PMID: 15938041]
[8]
Wu R, Liu X, Yin J, et al. IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting inflammasome in mice. Metabolism 2018; 83: 18-24.
[http://dx.doi.org/10.1016/j.metabol.2018.01.002] [PMID: 29336982]
[9]
Campos LP, Graciolo V, Sousa MM, et al. Research article polymorphisms rs1800795 of interleukin-6 and rs2228145 of interleukin-6 receptor genes in Euro-Brazilians with adult-onset type 1 diabetes mellitus. Genet Mol Res 2019; 18(3)
[http://dx.doi.org/10.4238/gmr18260]
[10]
Zhou J, Chen X, Ye H, et al. An association study between genetic polymorphism in the interleukin-6 receptor gene and coronary heart disease. BioMed Res Int 2014; 2014: 1-6.
[http://dx.doi.org/10.1155/2014/504727] [PMID: 24971337]
[11]
Chen B, Wu M, Zang C, Li Y, Xu Z. Association between il-6 polymorphisms and diabetic nephropathy risk: A meta-analysis. Am J Med Sci 2019; 358(5): 363-73.
[http://dx.doi.org/10.1016/j.amjms.2019.07.011] [PMID: 31451183]
[12]
Rafiq S, Frayling TM, Murray A, et al. A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects. Genes Immun 2007; 8(7): 552-9.
[http://dx.doi.org/10.1038/sj.gene.6364414] [PMID: 17671508]
[13]
Ferreira RC, Freitag DF, Cutler AJ, et al. Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases. PLoS Genet 2013; 9(4): e1003444.
[http://dx.doi.org/10.1371/journal.pgen.1003444] [PMID: 23593036]
[14]
Swerdlow DI, Holmes MV, Kuchenbaecker KB, et al. The interleukin-6 receptor as a target for prevention of coronary heart disease: A mendelian randomisation analysis. Lancet 2012; 379(9822): 1214-24.
[http://dx.doi.org/10.1016/S0140-6736(12)60110-X] [PMID: 22421340]
[15]
Zhang H, Zhao W, Liu B, et al. Il-6r protective variant rs7529229 reduces interleukin-6 signaling and contributes to a decreased ischemic stroke risk. Research Square 2020.
[16]
He F, Teng X, Gu H, et al. Interleukin-6 receptor rs7529229 T/C polymorphism is associated with left main coronary artery disease phenotype in a Chinese population. Int J Mol Sci 2014; 15(4): 5623-33.
[http://dx.doi.org/10.3390/ijms15045623] [PMID: 24699044]
[17]
Turolo S, Edefonti A, Lepore M, et al. SXR rs3842689: a prognostic factor for steroid sensitivity or resistance in pediatric idiopathic nephrotic syndrome. Pharmacogenomics 2016; 17(11): 1227-33.
[http://dx.doi.org/10.2217/pgs-2016-0029] [PMID: 27377607]

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