ABSTRACT
The elevated plasma homocysteine could adversely influence long-term renal graft survival by promoting vascular sclerosis in the kidney allograft. This could be mediated through endothelial dysfunction. A polymorphism C677T in the gene coding for the enzyme methylenetetrahydrofolate reductase [MTHFR] was identified. The aim of the present work was to study the influence of the C677T MTHFR gene polymorphism on total plasma homocysteine and folate levels in renal graft recipients, and its impact on chronic graft dysfunction and the associated endothelial dysfunction. Thirty two stable renal allograft recipients were included in this study [group I] and compared with age and sex matched thirty control subjects [group II]. Plasma homocysteine level, plasma folic acid level, plasma van Willebrand factor [vWF] activity together with endothelial dependent and independent brachial artery vascular responses were done for all subjects. MTHFR genotype was determined by PCR in all renal recipients who were further classified accordingly into 3 subgroups: [group Ia] with homozygous TT type, [group Ib] with heterozygous CT type, and [group Ic] is wild CC type. Renal allograft recipients showed significant higher level of homocysteine as compared to control group [44.42 +/- 32.08 vs 11.62 +/- 2.57 respectively, p<0.001]. There was significant endothelial dysfunction in the transplant group as evidenced by the higher vWF [119.71 +/- 17.71 vs 67.60 +/- 28.65 p<0.001] and poorer endothelial dependent dilatation [EDD] of the brachial artery [7.84 +/- 1.08 vs 12.68 +/- 0.96 p<0.001] as compared to the control group. There was significant negative correlation between plasma homocysteine level and creatinine clearance [r=-0.55, p=0.001], suggesting the deleterious effect of hyperhomocysteinaemia on graft function. The homozygous subgroup [gpIa] showed significant higher level of homocysteine, vWF, lower folic acid, creatinine clearance and EDD as compared to the other two subgroups [gp Ib and Ic]. Our study identified that the presence of hyperhomocysteinemia in combination with unfavorable MTHFR genotypes contributes to an increased risk for development of chronic allograft dysfunction