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Gene & Protein in Disease                                      Gene polymorphism and chronic kidney disease




            Table 3. Comparison of laboratory parameters between cases and controls
            Parameters                 Cases (N=62)             Controls (N=62)             Student’s t‑test
                                   Mean          SD          Mean           SD           T             P
            Urea (mg/dL)           126.31       38.71        27.09         5.18         20.004       <0.001
            Creatinine (mg/dL)      8.44        3.24          0.94         0.22         18.196       <0.001
            eGFR (mL/min/1.73 m )  16.613       7.30         92.53         23.27       −24.507       <0.001
                           2
            Spot urine (mg/g)      231.77       156.25       15.95         6.59         10.867       <0.001
            Calcium (mg/dL)         8.54        0.73          9.08         0.74         −4.052       <0.001
            Albumin (mg/dL)         3.39        2.94          3.77         0.43         −0.997        0.321
            Hemoglobin (g/dL)       9.45        1.76         13.23         1.93        −11.398       <0.001
            Notes: Student’s t-test was used for continuous variables. P<0.05 indicates a statistically significant difference. Abbreviations: eGFR: Estimated
            glomerular filtration rate; SD: Standard deviation.

            Table 4. Comparison of genotype and allele frequencies of   deterioration of renal functions, indicated by elevated
            CCR2 gene (rs1799864) between cases and controls   levels of urea, creatinine, spot urine, and decreased levels
                                                               of calcium and eGFR. Similar findings were observed
            Variable  Total (N=124)  Cases (N=62)  Controls (N=62)  by  Sezgin  et al.,  where  the  frequency  of  the  CCR2  GA
                      n      %    n     %      n      %        genotype was higher in cases, and the GG genotype was
            Genotype                                           higher in controls. The A allele was more frequent in
             GA       44    35.48  30  48.4    14     22.6     cases, and the G allele was more frequent in controls. The
             GG       80    64.52  32  51.6    48     77.4     results were statistically significant and consistent with the
                                                                          [16]
             AA        0     0    0     0.0    0      0.0      present study . Nakajima et al. reported that, although
                                        χ =9.018; P=0.003      CCR2 was not significantly associated with kidney disease,
                                        2
            Allele                                             the frequency of the A allele was higher in patients with
                                                               impaired kidneys . Similarly, in the present study, the
                                                                             [12]
             G      204   82.26   94   72.58   110   88.71     frequency of the A allele was observed to be higher in CKD
             A      44    17.74   30   27.42   14    11.29     patients (27.42%) than in non-CKD subjects (11.29%). In
                                        χ 7.073; P=0.007       another study by Elghoroury et al., the frequency of the A
                                         2=
            Notes: Chi-square (χ ) test was used to compare the CCR2 genotype   allele was significantly higher among children with ESRD.
                          2
            between chronic kidney disease cases and controls. P<0.05 indicates a   Moreover, they reported significantly higher frequencies
            statistically significant difference.              of the GA+AA genotype among transplantation,
                                                               hemodialysis, and ESRD patients, while the GG genotype
            to guide the clinical care of nephropathies, leading to   was more prevalent in controls .
                                                                                       [17]
            improvements  in  disease  surveillance,  drug  selection,
            diagnostic  accuracy,  and  family  counseling.  Accurate   Beyond  alterations  in  the  nucleotide  sequence,
            interpretation of genetic data is necessary for optimizing   epigenetic molecular mechanisms may play a critical role
                             [26]
            all of these processes . In the same context, the present   in the progression of renal disease through inflammation.
            study aimed to investigate the association of the CCR2 gene   Epigenetic mechanisms include  DNA methylation,
            polymorphism with CKD. For this purpose, 62  patients   histone  protein  modifications,  and  RNA  interference.
            with CKD (cases) and 62 age- and gender-matched non-  Epigenetic regulation of transcription plays a crucial
            CKD patients (controls) were enrolled in the study.  role in normal physiological development and also in
                                                               pathological conditions. For example, abnormal DNA
              In the present study on CCR2 polymorphism, the GG   methylation is linked to insulin resistance, inflammation,
            genotype was more prevalent in controls compared to   and immunological dysfunction. RNA interference
            cases (77.4% vs. 51.6%), whereas the GA genotype was   may significantly contribute to the development of
            more prevalent in cases (48.4%) compared to the controls   kidney disease, given the essential role of microRNAs
            (22.6%).  Moreover,  the  G  allele  was  more  prevalent  in   in maintaining glomerular homeostasis. Epithelial-
            controls (88.71%) compared to cases (72.58%), while   mesenchymal transition and subsequent renal tissue
            cases expressed the A allele (27.42%) more frequently   fibrosis are controlled by epigenetic changes. In CKD,
            than the controls (11.29%). The CCR2 GA genotype and   epimutations might occur due to uremic toxins, oxidative
            A allele were associated with the occurrence of CKD and   stress, inflammation, and hyperhomocysteinemia. Due


            Volume 2 Issue 4 (2023)                         5                        https://doi.org/10.36922/gpd.2253
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