Abstract
Background: End-stage renal disease (ESRD) is a chronic clinical condition that starts with an initial damage and ultimately develops into a complete loss of kidney function with an unknown mechanism. MMP-9C1562T (rs243866) and MMP-2G1575A (rs3918242) polymorphisms in the promoter region are associated with the incidence of many diseases including cardiovascular, hypertension, chronic kidney disease (CKD), and diabetes mellitus which result in ESRD. Objective: This study was conducted to investigate the possible effect of MMP-9C1562T and MMP-2G1575A polymorphisms on the incidence of ESRD in Kermanshah population as well as their correlation with the serum level of malondialdehyde (MDA). Materials and Methods: The present study was conducted through a case-control method. A total of 136 unrelated ESRD patients and 137 unrelated healthy individuals as the control group matched with patients based on the age and sex. MMP-9C1562T and MMP-2G1575Apolymorphisms were determined using the PCR-RFLP method and serum levels of MDA by High performance liquid chromatography. Results: We found that the frequency of MMP-9C1562T and MMP-2G1575A functional promoter genotypes and alleles in ESRD patients was significantly different compared to the control group. MMP-9C1562T and MMP-2G1575A alleles act synergistically to increase the risk of ESRD by 1.41 times (P = 0.008). In addition, results of this study demonstrated that there is a significant increase in the serum level of MDA in the presence of a dominant model of MMP-9 genotypes (T/T+ C/T vs C/C) and MMP-2 genotypes (A/A+G/A vs G/G) in ESRD patients compared to controls also increased the risk of ESRD 1.36 and 1.4 folds, respectively. Conclusion: We found in this study that MMP-9C1562T and MMP-2G1575A alleles synergistically increase the risk of ESRD but also raise the serum level of MDA in ESRD patients. This information may be important in the evaluation of ESRD progression and in the elucidation of the mechanisms of the disease pathogenesis. Further studies with larger sample sizes and different ethnicities are necessary to confirm these findings.
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