Presentation Authors: Aneesh Srivastava*, Narayan Prasad, Mansi Bhatt, Lucknow, India
Introduction: Allograft rejection remains to be one of the crucial impediments in successful renal transplantation. Matrix metalloproteinases (MMPs) play an important role in immune-mediated tissue destruction of the allograft by allowing influx of leucocytes and mononuclear cells into the graft and it appears that, the study of the role of MMPs in transplant rejection process may also lead to novel approaches in the therapy of rejection processes. The present study was, therefore, undertaken to investigate the association of functional polymorphisms in MMP-1 (-1607 1G/2G), (-519 A/G); MMP-3(5356 A/G), (1161 A/G) and MMP-9 (1721G/C), (Q279R A/G), (R668Q G/A) genes with risk of allograft rejection in renal transplant recipients of North India.
Methods: One hundred fifty live related renal transplant donors and recipients were genotyped for MMP-1, MMP-3 and MMP-9 gene polymorphisms by polymerase chain reactionâ€“restriction fragment length polymorphism methodology. Only sixty eight recipient samples were categorized into 57 non-rejecters and 11 rejecters and were analyzed further.
Results: The analysis showed that genotype frequencies of MMP1 (-1607 1G/2G) [2G/2G; OR = 2.97, 95% CI = 1.55-5.68, P = 0.001] and MMP9 (P574R) [CG; OR = 2.64, 95% CI = 1.62-4.32, P = 0.00 & GG; OR = 3.09, 95% CI = 1.10-8.63, P = 0.03] were significantly associated with allograft rejection. MMP1, 3 & 9 gene polymorphisms between rejecters and non-rejecters showed no significant difference. On comparison between non-rejecters and donors significantly reduced risk for allograft rejection was demonstrated in MMP-1 (-519 A/G) [AG; OR = 0.024, 95% CI = 0.003-0.182, P = 0.00], MMP-3(5356 A/G) [AG; OR = 0.228, 95% CI = 0.109-0.480, P = 0.00] and MMP-9(Q279R A/G) [AG; OR = 0.145, 95% CI = 0.064-0.329, P = 0.00] & (P574R G/C), [CG; OR = 0.183, 95% CI = 0.062-0.539, P = 0.002] while comparing for rejecters and donors a significant association was observed MMP9 (Q279R A/G) [AG; odds ratio (OR) = 0.089, 95% confidence intervals (95% CI) = 0.011-0.714, P = 0.023]
Conclusions: Mutant genotypes for MMP-1 (-519 A/G), MMP-3(5356 A/G) and MMP-9(Q279R A/G) & (P574R G/C) are associated with reduced risk for allograft rejection and improved allograft survival in North Indian transplant recipients and could serve as an ideal marker to predict pre-transplant allograft outcome.
Source of Funding: UPCST, Lucknow