Study of the Relation between Serum Total Homocysteine and Methylenetetrahydrofolate Reductase Gene Polymorphism In Renal Transplant Recipients | ||||
Bulletin of Egyptian Society for Physiological Sciences | ||||
Article 8, Volume 32, Issue 1, June 2012, Page 111-123 PDF (193.74 K) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/besps.2012.35539 | ||||
View on SCiNiTO | ||||
Authors | ||||
Hala El-Wakil* 1; Iman Diab2; Gihan Sharara2; Sahar Azab3; Samer Zahran4 | ||||
1Department of Internal Medicine, Faculty of Medicine, Alexandria University, Egypt | ||||
2Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Egypt | ||||
3Department of Cardiology, Faculty of Medicine, Alexandria University, Egypt | ||||
4Department of Biochemistry, Faculty of Pharmacy, Pharos University | ||||
Abstract | ||||
The main cause of reduced long-term graft survival is chronic allograft injury. Cardiovascular risk factors such as hyperhomocysteinemia seem to play an important role. As atherosclerotic lesions in chronic allograft injury may be due to hyperhomocysteinemia, we examined the hypothesis that the C677T variant of the methylenetetrahydrofolate reductase (MTHFR) gene, which is linked to elevated plasma homocysteine levels in patients with renal failure, determines renal allograft dysfunction. Endothelial dysfunction probably has a role in this process. The aim of the present work was to study the influence of the C677T MTHFR gene polymorphism on plasma levels of homocysteine and folate in renal graft recipients, and their impact on chronic graft dysfunction, as well as studying the relation between chronic allograft injury and endothelial dysfunction by estimating von Willebrand factor (vWF) and measuring endothelial dependent dilatation of the brachial artery (EDD). The subjects included in this study were 32 renal allograft recipients (Group I) and 30 normal subjects as a control group (Group II). MTHFR genotype was determined by PCR, subsequently the patients were further classified into three subgroups according to the MTHFR genotypes: Group I (a): 6 allograft recipients with homozygous- TT type. Group I (b): 8 allograft recipients with heterozygous- CT type. Group I (c): 18 allograft recipients with wild- CC type. Estimation of total plasma homocysteine concentration, plasma folic acid, plasma and von Willebrand factor (vWF) were determined. Vascular responses of the brachi al artery were performed by high resolution ultrasound imaging. This study showed significantly higher levels of both homocysteine and von Willebrand factor (vWF) were found in renal allograft recipients as compared to the control group. A negative correlation was found between homocysteine levels and creatinine clearance suggesting hyperhomocysteinemia contributes to the renal allograft dysfunction. No significant difference was found as regards the plasma folic acid levels between the patients and controls. Allograft recipients with MTHFR homozygous-TT type showed significantly higher levels of homocysteine and vWF as compared to allograft recipients with heterozygous-CT type and those with wild- CC type. Also allograft recipients with homozygous- TT type showed lower levels of plasma folic acid and creatinine clearance as compared to the other two subgroups. Lower endothelial dependent dilatation of the brachial artery (EDD) was observed in renal allograft recipients as compared to the control group. The EDD was significantly less in allograft recipients with MTHFR homozygous- TT type than those with MTHFR heterozygous- CT type or wild- CC type. CONCLUSION: The present study supports the hypothesis that the C677T variant of the MTHFR gene is an important determinant of renal-transplant survival, and that certain genotypes of MTHFR gene are associated with chronic allograft injury. Hyperhomocysteinemia, elevated vWF, lower folic acid levels and endothelial dysfunction together with certain genotypes of MTHFR gene increases the risk of development of chronic allograft injury in renal transplant patients. | ||||
Keywords | ||||
renal transplant; MTHF gene polymorphism; Homocysteine; Folic acid; Von Willebrand Factor; endothelial dysfunction | ||||
Statistics Article View: 86 PDF Download: 152 |
||||