Abstract
Purpose
Engulfment and cell motility 1 (ELMO1), is a candidate gene responsible for cell motility and phagocytosis. However, its role in the development and progression of nephropathy attributed to T2D is still unknown. Kidney injury molecule-1 (KIM-1) plays a significant role in renal regeneration processes. The current study aimed to evaluate the association between kidney injury molecule-1 levels, ELMO1 gene polymorphism (rs741301, and rs1345365) as well as DN in an Egyptian population with T2D.
Methods
In this study, we enrolled 89 participants from the internal medicine outpatient clinic, 23 T2DM without DN, 22 with DN, and 44 control subjects. They were genotyped by real-time PCR. Serum level of KIM-1 was detected by ELISA.
Results
Serum KIM-1 level was correlated with DM duration, HbA1C, and UACR (P value <0.001) in T2D. There was no significant difference in the allelic and genotypic frequencies of rs741301 and rs1345365 between participants with DM who presented with albuminuria and those without. Results showed that rs1345365A/rs741301T and rs1345365G/rs741301C haplotypes were more common in patients with T2D than in HCs. However, the difference was not statistically significant (P = 0.262 and 0.414, respectively).
Conclusions
KIM-1 can be a useful non-invasive biomarker for detecting early DN. The association between ELMO1 gene polymorphisms and the risk of DN in patients with T2D was not validated. Therefore, further studies with a larger sample size must be conducted.
Similar content being viewed by others
References
Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88–98.
Temelkova-Kurktschiev T, Stefanov T. Lifestyle and genetics in obesity and type 2 diabetes. Exp Clin Endocrinol Diabetes. 2012;120:1–6.
Singh G, Sharma R, Raina P, et al. Association of Genetic Variants of ELMO1 gene with diabetic nephropathy in the north Indian Population, 2020 , PREPRINT (Version 1) available at Research Square. https://doi.org/10.21203/rs.3.rs-121795/v1.
Mehrabzadeh M, Pasalar P, Karimi M, Abdollahi M, Daneshpour M, Asadolahpour E, Razi F. Association between ELMO1 gene polymorphisms and diabetic nephropathy in an Iranian population. J Diabetes Metab Disord. 2016;7(15):43.
Shimazaki A, Tanaka Y, Shinosaki T, Ikeda M, Watada H, Hirose T. ELMO1 increases expression of extracellular matrix proteins and inhibits cell adhesion to ECMs. Kidney Int. 2006;70:1769–76.
Meersch M, Schmidt C, Van Aken H, et al. A Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. 2014;9(3):e93460. https://doi.org/10.1371/journal.pone.0093460
Khan FA, Fatima SS, Khan GM, Shahid S. Evaluation of kidney injury molecule-1 as a disease progression biomarker in diabetic nephropathy. Pakistan J Med Sci. 2019;35:992–6.
American Diabetes Association Diabetes Care 2019 42: S13–S28. https://doi.org/10.2337/dc19-S002.
Ivanac-Janković R, Lovčić V, Magaš S, Šklebar D, Kes P. The novella about diabetic nephropathy. Acta Clin Croat. 2015;54:83–91.
Nogare AL, Veronese FV, Carpio VN, et al. Kidney injury molecule-1 expression in human kidney transplants with interstitial fibrosis and tubular atrophy. BMC Nephrol. 2015;16:19.
Hathaway CK, Chang AS, Grant R, et al. High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy. Proc Natl Acad Sci U S A. 2016;113:2218–22.
Yang C, Sorokin A. Upregulation of fibronectin expression by COX-2 is mediated by interaction with ELMO1. Cell Signal. 2011;23:99–104.
Wei L, Xiao Y, Li L, Xiong X, Han Y, Zhu X, Sun L. The susceptibility genes in diabetic nephropathy. Kidney Dis (Basel). 2018;4:226–37.
El-Ashmawy NE, El-Zamarany EA, Khedr NF, El-Fattah AIA, Eltoukhy SA. Kidney injury molecule-1 (Kim-1): an early biomarker for nephropathy in type II diabetic patients. International J Diabet Devel Count. 2015;35:431–8.
Conway BR, Manoharan D, Manoharan D, et al. Measuring urinary tubular biomarkers in type 2 diabetes does not add prognostic value beyond established risk factors. Kidney Int. 2012;82(7):812–8.
Sinkala M, Zulu M, Kaile T, et al. Performance characteristics of kidney injury molecule-1 in relation to creatinine, urea, and microalbuminuria in the diagnosis of kidney disease. Int J Appl Basic Med Res. 2017;7:94–9.
Chaudhary K, Phadke G, Nistala R, Weidmeyer CE. The emerging role of biomarkers in diabetic and hypertensive chronic kidney disease. Curr Diab Rep. 2010;10:37–42.
Hanson RL, Millis MP, Young NJ, et al. E LMO1 variants and suscep-tibility to diabetic nephropathy i n American Indians. Mol GenetMetab. 2010;101:383–90.
Kim S, Abboud HE, Pahl MV, et al. Examination of association with candidate genes for diabetic nephropathy in a Mexican American population. Clin J Am Soc Nephrol. 2010;5(6):1072–8.
Bayoumy NMK, El-Shabrawi MM, Leheta OF, Abo El-Ela AEM, Omar HH. Association of ELMO1 gene polymorphism and diabetic nephropathy among Egyptian patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2020;36:e3299.
Wu H, Wang Y, Chen M, et al. Association of ELMO1 gene polymorphisms with diabetic nephropathy in Chinese population. J Endocrinol Investig. 2013;36(5):298–302.
Topete-González LR, Ramirez-Garcia SA, Charles-Niño C, Villa-Ruano N, Mosso-González C, Dávalos-Rodríguez NO. Polimorfismo g.37190613 G>A del gen ELMO1 en población Mexicana, marcador potencial para la patología clínico-quirúrgica [Polymorphism g.37190613 G>A of the ELMO1 gene in the Mexican population: potential marker for clinical-surgical pathology]. Cir Cir. 2014;82(4):402–11.
Acknowledgments
We would like to thank Dr. Shaymaa Al-Shahat Abada for her help in collecting blood samples from the participants.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Financial interests
The authors declare they have no financial interests.
The authors have no relevant financial or non-financial interests to disclose.
Conflicts of interests/Competing interests
The authors have no competing interests to declare that are relevant to the content of this article.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
El Nahid, M.S., Al-Ganiny, A.F.M. & Youssef, R.N. Association between engulfment and cell motility 1-gene polymorphisms and diabetic nephropathy in an Egyptian population with type 2 diabetes. J Diabetes Metab Disord 21, 439–444 (2022). https://doi.org/10.1007/s40200-022-00990-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40200-022-00990-9