Chemokine Receptor 2 (Ccr2) G190a Polymorphism in Chronic Renal Failure Patients Requiring Hemodialysis

Abstract

End-stage renal disease is associated with the inflammatory state characterized by infiltrating macrophages/lymphocytes, a major source of chemokines. The aim of this study was to determine the association of CCR2 G190A polymorphism in patients with chronic renal failure (CRF) requiring hemodialysis. Seventy CRF patients and thirty healthy controls were enrolled in the current study; PCR-RFLP technique was used to assess the gene frequencies of CCR2 G190A. The results of the present study showed that there was a significant difference in the genotype and allele frequency distribution of CCR2 G190A in CRF patients and control subjects. A significant association was found between CCR2 G190A and CRF risk, especially, the AA genotype (OR= 2.5, 95% CI=0.26-23.66) and A allele (OR=2.9, 95% CI=1.14-7.3). The polymorphism was significantly associated with the presence of diabetes mellitus. From this study, it could be concluded that, a significant association was found between the AA genotype of CCR2 G190A polymorphism and CRF. Other chemokine polymorphisms in renal pathologies have to be further investigated with larger population based studies.

An African perspective on the genetic risk of chronic kidney disease: a systematic review

“…Of the thirteen studies included, kidney dysfunction was characterized mainly by an estimated glomerular filtration rate (eGFR) equal to or less than 60 ml/min/1.73m 2 [ 18 , 23 , 25 , 27 , 28 ]. The remaining studies used other surrogate measures to determine kidney dysfunction, which included ESRD (undergoing haemodialysis) [ 19 , 21 , 22 , 24 , 26 ], elevated serum creatinine levels [ 20 ] and a combination of serum creatinine levels greater or equal to 170 μmol/l and dipstick proteinuria greater or equal to 2 [ 30 ] or serum creatinine above 1.4 mg/dl (men) and 1.2 mg/dl (women) and urinary albumin to creatinine ratio (ACR) above 30 mg/g [ 29 ]. The CKD patients included in these studies were of different aetiologies, reflective of the diversity in nephropathy present in Africa.…”

“…According to the studies included in this review, some SNP’s investigated in the MYH9 [ 28 ], AT1R [ 19 ], and MTHFR [ 20 ] genes failed to predict prevalent CKD, ESRD or related traits (serum creatinine, eGFR and ACR), while variants in the APOL1 [ 27 , 29 , 30 ], apoE [ 21 ], eNOS [ 18 , 20 ], XPD [ 22 ], XRCC1 [ 22 ], renalase [ 23 , 26 ], ADIPOQ [ 31 ] and CCR2 [ 24 ] genes were associated with either prevalent CKD or progression of CKD, ESRD, or other surrogate measures of renal function.…”

“…This study suggested that the +276G > T allele may indirectly contribute to CKD susceptibility by increasing adiponectin levels (p = 0.04). Elhelbawy et al [ 24 ] found a significant association between CCR2 –641 and chronic renal failure, particularly the AG genotype (OR = 2.8, 95% CI = 1.40–5.51), combined AG and GG genotypes (OR = 4.1, 95% CI = 1.27–13.03) and A allele (OR = 2.9, 95% CI = 1.14–7.3).…”

“…Currently, the role of the polymorphisms in the apoE [ 21 ], eNOS [ 18 , 20 ], XPD [ 22 ], XRCC1 [ 22 ], renalase [ 23 , 26 ], ADIPOQ [ 31 ] and CCR2 [ 24 ] genes in the aetiology of CKD remains controversial and further larger studies should be conducted to confirm these results in population groups within Africa. Certainly, various polymorphisms have been associated, both directly and indirectly, with increased CKD risk in certain populations and decreased CKD risk in others or alternatively have no convincing association.…”