Impact of MMP2, MMP9 and TIMP2 Gene Polymorphisms on Allograft Rejection in Pediatric Renal Transplant Recipients

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Abstract

Introduction

Acute and chronic allograft rejection has been continuously an important obstacle in the follow up of renal transplant recipients. During the clinical management, several factors acting simultaneously result in acute rejection and chronic allograft nephropathy. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are responsible for the organization of extracellular matrix. They play role in cell proliferation and cellular invasion. Changes in MMP expression levels have been reported to be associated with renal allograft rejection and interstitial fibrosis. In the current study, we aimed to investigate functional polymorphisms of MMP2, MMP9 and TIMP2 genes in pediatric renal transplant recipients.

Materials and Methods

A total of 68 kidney transplant recipients and 58 controls were enrolled in the current study. Kidney transplant recipient group was also divided into two subgroups: non-rejecters (n=47), and rejecters (n=21). The MMP2 -735C>T (rs2285053), MMP2 -1306C>T (rs243865), MMP2 -1575G>A (rs243866), MMP9 -1562C>T (rs3918242), TIMP2 -418G>A (rs8179090) and TIMP2 -303C>T (rs2277698) polymorphisms were analyzed by using polymerase chain reaction and restriction fragment length polymorphism methods. Allelic prevalence was compared with reference values of control group and Hardy-Weinberg equilibrium was tested.

Results

The mean age of the study group was 16.7±3.9 and the control group was 14.8±5.6 years. Mean follow-up time after transplantation was 37.7±7.9 months. We compared the allele frequencies in the two groups and calculated a statistically significant difference in rs2285053, rs243865, rs243866, rs3918242, rs8179090 and rs2277698 polymorphisms frequencies between the transplant recipients and controls. When the transplant recipient group was compared in itself regarding allograft rejection, all investigated polymorphisms but TIMP2 -418G>A (rs8179090) revealed a statistically significant difference between rejecters and non-rejecters (p<0.05).

Discussion

In our cohort, functional polymorphism of MMP2, MMP9 and TIMP2 genes revealed different allele frequencies in the pediatric renal transplant and control patients as well as in allograft rejection and non-rejection patients in the study group. Previously, expression profiles of these genes and proteins have been reported in transplant recipients. To our knowledge, this is the first study investigating functional MMP2, MMP9 and TIMP2 polymorphisms in pediatric kidney recipients.

Conclusion

MMPs and their tissue inhibitors could be important predictive biological markers for follow up of kidney transplant recipients.

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