Polymorphisms in the methylenetetrahydrofolate reductase gene are determinant for vascular complications after liver transplantation

Eur J Clin Nutr. 2008 Mar;62(3):430-5. doi: 10.1038/sj.ejcn.1602699. Epub 2007 Feb 21.

Abstract

Objective: The aim of this study was to evaluate the role of the C677T-MTHFR (methylenetetrahydrofolate reductase)-polymorphism (CC, CT and TT) for vascular complications in liver transplant recipients.

Design: Retrospective study.

Setting: Hepatology-Transplantation-Unit, Johann Wolfgang Goethe-University, Frankfurt am Main.

Subjects: 48 liver transplant recipients were included, no dropouts.

Methods: MTHFR polymorphism was detected by PCR amplification and digestion with Hinfl restriction enzyme. Vascular complications after liver transplantation were detected from the patients' records. The total serum homocysteine (HCY) was analyzed with high-pressure liquid chromatography.

Results: In the wild-type group (CC), the HCY levels were slightly high (14.0+/-1 micro M). Among the patients with the CT polymorphism, the HCY values were elevated (22.5+/-3 micro M). In the homozygous TT group, there was a significant increase (31.2+/-6 micro M, P<0.01) of the HCY values. The percentage of vascular complications was higher in the heterozygous CT (47%) and homozygous TT (62.5%) group compared with wild-type CC (21%). Patients with a homozygous TT genotype of the MTHFR polymorphism with a vascular complication had a highly significant elevated HCY level compared to the other genotype groups, both with and without any vascular complications (P<0.001). Recipients with an elevated HCY and the TT polymorphism have a higher probability of developing a vascular complication after transplantation (odds ratio: 4.3 and 11.0; 95% confidence interval: 1.15, 12.25 and 1.41, 85.24).

Conclusions: The C677T polymorphism in the MTHFR gene and subsequent elevation of the total serum HCY is significantly associated with an increased incidence of vascular complications in liver transplant recipients.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Homocysteine / blood*
  • Humans
  • Liver Transplantation* / adverse effects
  • Liver Transplantation* / physiology
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Retrospective Studies
  • Risk Factors
  • Vascular Diseases / enzymology
  • Vascular Diseases / etiology
  • Vascular Diseases / genetics*

Substances

  • Homocysteine
  • Methylenetetrahydrofolate Reductase (NADPH2)