Matrix metalloproteinase (MMP-9 and MMP-2) gene polymorphisms influence allograft survival in renal transplant recipients

Abstract

Matrix metalloproteinases (MMPs), especially basement membrane-degrading MMP-9 and MMP-2, play an important role in immune-mediated tissue destruction of the allograft by allowing influx of leucocytes and mononuclear cells into the graft. The present study was, therefore, undertaken to investigate the association of functional polymorphisms in MMP-9 (836A>G, 1721G>C and 2003G>A) and MMP-2 (-735C>T) genes with risk of allograft rejection in renal transplant recipients of North India. Three hundred and six renal transplant recipients categorized into 228 non-rejecters and 78 rejecters were genotyped for MMP-9 and MMP-2 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism methodology. A significant difference in genotype/allele frequencies was observed between healthy individuals in comparison to non-rejecters/rejecters for MMP-9 836A>G, MMP-9 2003G>A and MMP-2 -735C>T. Mutant allele carriers for MMP-9 2003G>A [GA+AA-; odds ratio (OR) = 0.45, 95% confidence intervals (95% CI) = 0.24-0.85, P = 0.014] and MMP-2 -735C>T (CT+TT-; OR = 0.40, 95% CI = 0.18-0.91, P = 0.029) demonstrated significantly reduced risk for allograft rejection. The mean time to first rejection episode was significantly higher in GA/AA and CT/TT genotype recipients for MMP-9 2003G>A (log P = 0.026) and MMP-2 -735C>T (log P = 0.003), respectively. Haplotypes with mutant alleles for MMP-9 1721C>G-2003G>A and mutant allele genotype combinations for both MMP-9 2003G>A and MMP-2 -735C>T conferred significantly reduced risk for allograft rejection. Mutant alleles for MMP-9 2003G>A and MMP-2 -735C>T 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.