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Gene & Protein in Disease Gene polymorphism and chronic kidney disease

often under-recognized by both patients and clinicians [2,3] . CCR2 is a chemokine receptor of the monocyte
Ironically, CKD prevalence is more commonly reported in chemoattractant protein 1 (MCP1), a member of the
low- and middle-income countries than in high-income chemotactic cytokines (CC) family of chemokines,
countries . CKD is defined as the presence of kidney primarily expressed on monocytes . The CCR2
[4]
[15]
damage or an estimated glomerular filtration rate (eGFR) chemokine receptor mediates leukocyte chemoattraction
<60 mL/min/1.73 m , persisting for 3 months or more, during the initiation and amplification phases of renal
2
irrespective of the cause . The progression of CKD leads inflammation . The CCR2 protein consists of 374 amino
[5]
[16]
to a loss in kidney function, ultimately resulting in the need acids, and the CCR2-V64I polymorphism is a transition
for dialysis or renal replacement therapy. Given the poor mutation that changes valine to isoleucine at position 64 of
prognosis associated with CKD, early diagnosis and disease the CCR2 receptor .
[17]
screening are crucial for managing its prevalence. CKD
frequently coexists with diabetes and/or hypertension, Recent findings underscore the therapeutic importance
though other causes such as glomerulonephritis, infection, of chemokines in chronic renal failure, due to their
[18]
and environmental exposures are also prevalent in Asia, pivotal role in disease pathogenesis through CCL2, the
sub-Saharan Africa, and other developing countries . ligand of the CCR2 receptor. CCL2 has been implicated
[6]
Much like in Western countries, nearly half of the CKD as a key mediator of CKD in both human and animal
[19-22]
cases in India are attributed to diabetes and hypertension . models . In addition, pharmacological inhibition of
[7]
Contemporary studies have reported a CKD prevalence CCL2 has demonstrated efficacy in reducing chronic
[23]
rate of 17.5% [8,9] , a figure driven by the rising incidence of renal damage in lupus nephritis , improving podocyte
diabetics and hypertension in the country. The prevalence function in diabetic nephropathy, and improving renal
[24]
of CKD in India exceeds the global average, highlighting function in diabetic patients with albuminuria . Given
the need for further studies to evaluate prognosis, markers, the importance of CCR2 and its ligand-mediated effect
and associated comorbidities. in kidney pathophysiology, the present case–control
study aimed to investigate the association of CCR2 gene
The pathophysiological mechanisms of CKD result in polymorphism with susceptibility to CKD in the North
a progressive loss of renal function due to factors such Indian population.
as tubulointerstitial fibrosis, hypoxia-induced interstitial
capillary damage, renal tubule destruction, and loss of 2. Materials and methods
functional nephrons. Locally produced chemokines
exacerbate renal damage in CKD through profibrotic 2.1. Study population
and inflammatory mechanisms. It is essential to interrupt This case–control study involved 62 North Indian patients
the chemokine signal to reduce inflammation . The with CKD, 62.9% of whom were men. Subjects were recruited
[10]
recruitment of macrophages to the kidney in nephropathy from the Department of Medicine at Era’s Medical College
is mostly dependent on the chemokine ligand 2/chemokine and Hospital, Lucknow, India. The diagnosis of CKD was
receptor 2 (CCL2/CCR2) signaling pathway. Treatment established based on eGFR and albuminuria, with eGFR
with the CCR2 antagonist RS504393 dramatically calculated using the Cockcraft-Gault formula and serum
decreased infiltrating macrophages in diabetic mouse creatinine levels. Further, classification of CKD followed
(db/db) mice, enhanced insulin resistance, and improved the Kidney Disease Outcomes Quality Initiative (KDOQI)
albuminuria, thereby mitigating renal injury . Thus, for criteria for stages of CKD. Patients were divided according
[11]
a deeper comprehension of the disease mechanism, it is to eGFR into different stages: non-end-stage renal disease
essential to identify genetic variations in chemokines and (non-ESRD) (grades 1 – 4, eGFR 15 – 90 mL/min/1.73 m )
2
their functional impact on disease status. and end-stage renal disease (ESRD) stage (grade 5; eGFR
2 [25]
Polymorphisms in chemokine genes may cause < 15 mL/min/1.73 m ) . A total of 62 healthy unrelated
interindividual differences in transcriptional control, individuals with normal renal function (56.5% of whom
resulting in a variable synthesis of pro-inflammatory were men) from the same geographic location were
molecules. Single-nucleotide polymorphisms (SNPs) in included as controls, excluding those who suffered from
the CCR2 gene have been implicated in various diseases acute kidney injury, cardiovascular disease, sepsis, or were
in multiple studies, including CKD, diabetic nephropathy, critically ill. The study was approved by the Institutional
immunoglobulin A nephropathy, and hypertension [10,12-14] . Ethical Committee of Era’s Lucknow Medical College and
These studies collectively suggest that SNPs in the CCR2 gene Hospital. This study was conducted in conformity with
may play a role in CKD, potentially influencing inflammation the Declaration of Helsinki, and informed consent was
and oxidative stress. However, further research is needed to obtained from all subjects before sample collection. After
fully understand the impact of these SNPs on CKD. obtaining written informed consent and a detailed history,

Volume 2 Issue 4 (2023) 2 https://doi.org/10.36922/gpd.2253