AccScience Publishing / GPD / Volume 2 / Issue 4 / DOI: 10.36922/gpd.2253
Cite this article
77
Download
720
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Association of CCR2 gene polymorphism with chronic kidney disease in the North Indian population

Aseem Yadav1 Saliha Rizvi2* Devendra Kumar1 Syed Tasleem Raza3 Jalees Fatima1 Farheen Khan2 Ajay Mishra1
Show Less
1 Department of Medicine, Era’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
2 Department of Biotechnology, Era University, Lucknow, Uttar Pradesh, India
3 Department of Biochemistry, Era’s Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
Submitted: 15 November 2023 | Accepted: 5 January 2024 | Published: 10 January 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Chronic kidney disease (CKD), characterized by decreased renal function, is associated with an underlying elevated renal inflammatory state. The chemokine receptor 2 (CCR2) mediates leukocyte chemoattraction in the initiation and amplification phases of renal inflammation. In this study, which involved 62 patients and 62 controls, we aim to elucidate the association between the CCR2 G190A (rs1799864) polymorphism and CKD. Polymerase chain reaction-restriction fragment length polymorphism technique-based single-nucleotide polymorphism genotyping of the CCR2 gene (rs1799864) was used to assess the allele and genotype frequencies of CCR2. The Chi-square test was used to assess the potential association between G190A polymorphism and CKD, including its stages. The presence of the CCR2 G190A polymorphism was significantly associated with CKD. The results unveiled a significant difference in the genotype and allele frequency distribution of CCR2 G190A in CKD patients and control subjects. CCR2 GA genotype (P = 0.003) and A allele (P = 0.007; odds ratio [OR] = 0.40; 95% confidence interval [CI] = 0.20 – 0.80) were found to be significantly associated with CKD. A significant association was identified between genotype and stage of CKD, with the GA genotype more common among end-stage renal disease (ESRD) (stage 5) and the GG genotype among non-ESRD (stages 1 – 4) patients (P < 0.001). The polymorphism was significantly associated with deteriorating renal function, as evidenced by elevated levels of serum urea, serum creatinine, and spot urine, alongside a decrease in serum calcium and estimated glomerular filtration rate. The study revealed that the GA genotype of CCR2 is associated with CKD, ESRD, severe albuminuria, and renal dysfunction. However, no association was observed between the CCR2 gene polymorphism and the causes of CKD in the North Indian population.

Keywords
Chronic kidney disease
End-stage renal disease
Chemokine receptor-2
Single-nucleotide polymorphism
Polymerase chain reaction-restriction fragment length polymorphism
Funding
None.
References
  1. Sarnak MJ, Levey AS, Schoolwerth AC, et al., 2003, Kidney disease as a risk factor for development of cardiovascular disease: A statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation, 108(17): 2154–2169. https://doi.org/10.1161/01.CIR.0000095676.90936.80

 

  1. Coresh J, Selvin E, Stevens LA, et al., 2007, Prevalence of chronic kidney disease in the United States. JAMA, 298(17): 2038–2047. https://doi.org/10.1001/jama.298.17.2038

 

  1. Plantinga LC, Boulware LE, Coresh J, et al., 2008, Patient awareness of chronic kidney disease: Trends and predictors. Arch Intern Med, 168(20): 2268–2275. https://doi.org/10.1001/archinte.168.20.2268

 

  1. Mills KT, Xu Y, Zhang W, et al., 2015, A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010. Kidney Int, 88(5): 950–957. https://doi.org/10.1038/ki.2015.230

 

  1. Chapter 1: Definition and classification of CKD. Kidney Int Suppl (2011), 2013, 3(1): 19–62. https://doi.org/10.1038/kisup.2012.64

 

  1. Jha V, Garcia-Garcia G, Iseki K, et al., 2013, Chronic kidney disease: Global dimension and perspectives. Lancet, 382(9888): 260–272. https://doi.org/10.1016/S0140-6736(13)60687-X

 

  1. Rajapurkar MM, John GT, Kirpalani AL, et al., 2012, What do we know about chronic kidney disease in India: First report of the Indian CKD registry. BMC Nephrol, 13: 10. https://doi.org/10.1186/1471-2369-13-10

 

  1. Singh AK, Farag YM, Mittal BV, et al., 2013, Epidemiology and risk factors of chronic kidney disease in India - results from the SEEK (Screening and Early Evaluation of Kidney Disease) study. BMC Nephrol, 14: 114. https://doi.org/10.1186/1471-2369-14-114

 

  1. Varma PP, 2015, Prevalence of chronic kidney disease in India - Where are we heading? Indian J Nephrol, 25(3): 133–135.

 

  1. Alkady MM, Abdel-Messeih PL, El-Fishawy HS, et al., 2020, Evaluation of chemokine receptor 2 polymorphism in patients with end-stage renal disease. J Egypt Soc Nephrol Transpl, 20(3): 151–156. https://doi.org/10.4103/jesnt.jesnt_2_20

 

  1. Li HD, You YK, Shao BY, et al., 2022, Roles and crosstalks of macrophages in diabetic nephropathy. Front Immunol, 13: 1015142. https://doi.org/10.3389/fimmu.2022.1015142

 

  1. Nakajima K, Tanaka Y, Nomiyama T, et al., 2002, Chemokine receptor genotype is associated with diabetic nephropathy in Japanese with type 2 diabetes. Diabetes, 51(1): 238–242. https://doi.org/10.2337/diabetes.51.1.238

 

  1. Gao J, Liu X, Wei L, et al., 2016, Genetic variants of MCP-1 and CCR2 genes and IgA nephropathy risk. Oncotarget, 7: 77950–77957. https://doi.org/10.18632/oncotarget.12847

 

  1. Zhang M, Ardlie K, Wacholder S, et al., 2006, Genetic variations in CC chemokine receptors and hypertension. Am J Hypertens, 19(1): 67–72. https://doi.org/10.1016/j.amjhyper.2005.06.025

 

  1. Kitagawa K, Wada T, Furuichi K, et al., 2004, Blockade of CCR2 ameliorates progressive fibrosis in kidney. Am J Pathol, 165(1): 237–246. https://doi.org/10.1016/S0002-9440(10)63292-0

 

  1. Sezgin I, Koksal B, Bagci G, et al., 2011, CCR2 polymorphism in chronic renal failure patients requiring long-term hemodialysis. Intern Med, 50(21): 2457–2461. https://doi.org/10.2169/internalmedicine.50.5119

 

  1. Elghoroury EA, Elshamaa MF, Fadel FI, et al., 2018, CCR2 V64I genotyping: Impact on end stage renal disease development, progression and renal transplantation outcome. JIBPS, 5(4): 5–11.

 

  1. Anders HJ, Vielhauer V, Schlöndorff D, 2003, Chemokines and chemokine receptors are involved in the resolution or progression of renal disease. Kidney Int, 63(2): 401–415. https://doi.org/10.1046/j.1523-1755.2003.00750.x

 

  1. Kashyap S, Warner GM, Hartono SP, et al., 2016, Blockade of CCR2 reduces macrophage influx and development of chronic renal damage in murine renovascular hypertension. Am J Physiol Renal Physiol, 310(5): F372–F384. https://doi.org/10.1152/ajprenal.00131.2015

 

  1. Matsunaga N, Ikeda E, Kakimoto K, et al., 2016, Inhibition of G0/G1 switch 2 ameliorates renal inflammation in chronic kidney disease. eBioMedicine, 13: 262–273. https://doi.org/10.1016/j.ebiom.2016.10.008

 

  1. Eardley KS, Zehnder D, Quinkler M, et al., 2006, The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease. Kidney Int, 69(7): 1189–1197. https://doi.org/10.1038/sj.ki.5000212

 

  1. Tesch GH, 2008, MCP-1/CCL2: A new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol, 294(4): F697–F701. https://doi.org/10.1152/ajprenal.00016.2008

 

  1. Kulkarni O, Pawar RD, Purschke W, et al., 2007, Spiegelmer inhibition of CCL2/MCP-1 ameliorates lupus nephritis in MRL-(Fas)lpr mice. J Am Soc Nephrol, 18(8): 2350–2358. https://doi.org/10.1681/ASN.2006121348

 

  1. Boels MGS, Koudijs A, Avramut MC, et al., 2017, Systemic monocyte chemotactic protein-1 inhibition modifies renal macrophages and restores glomerular endothelial glycocalyx and barrier function in diabetic nephropathy. Am J Pathol, 187(11): 2430–2440. https://doi.org/10.1016/j.ajpath.2017.07.020

 

  1. National Kidney Foundation, 2002, K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis, 39: S1–S266.

 

  1. Köttgen A, Gall ECL, Halbritter J, et al., 2022, Genetics in chronic kidney disease: Conclusions from a kidney disease: Improving Global Outcomes (KDIGO) controversies conference. Kidney Int, 101(6): 1126–1141. https://doi.org/10.1016/j.kint.2022.03.019

 

  1. Dwivedi RS, Herman JG, McCaffrey TA, et al., Beyond genetics: Epigenetic code in chronic kidney disease. Kidney Int, 79(1): 23–32. https://doi.org/10.1038/ki.2010.335
Conflict of interest
The authors declare that they have no competing interests.
Share
Back to top
Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing