Clinical Nephrology – Epidemiology – Clinical Trials
Kidney International (2005) 67, 1980–1985; doi:10.1111/j.1523-1755.2005.00298.x
Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients
WOLFGANG C WINKELMAYER, ANDREA HUBER, OSWALD F WAGNER, WALTER H HÖRL, GERE SUNDER-PLASSMANN and MANUELA FÖDINGER
Division of Pharmacoepidemiology and Pharmacoeconomics and the Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria; and the Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
Correspondence: Manuela Födinger, M.D., Clinical Institute of Medical and Chemical Laboratory Diagnostics Medical University Vienna Währinger Gürtel 18–20 A-1090 Wien, Austria. E-mail:manuela.foedinger@meduniwien.ac.at
Received 2 September 2004; Revised 4 November 2004; Accepted 9 December 2004.
Abstract
Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B12 in kidney transplant recipients.
Background
Currently, no evidence is available on the putative associations between a novel single nucleotide polymorphism of the 5,10-methylenetetrahydrofolate reductase gene MTHFR 1793G>A and plasma levels of vitamin B12, folate, or total homocysteine (tHcy).
Methods
In a cross-sectional study of 730 kidney allograft recipients, patients were categorized by MTHFR 1793G>A genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B12, folate, and tHcy plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of MTHFR 1793G>A and these three dependent variables. As hypothesized in previous work, we specifically evaluated possible effect modification between the MTHFR 1793G>A and 1298A>C mutations on these outcomes.
Results
The allele frequency for MTHFR 1793G>A was 0.052. Heterozygosity (N = 72) or homozygosity (N = 2) for MTHFR 1793G>A was not independently associated with plasma levels of vitamin B12 (P = 0.33) or tHcy (P = 0.70), but a borderline association with higher folate concentrations was detected (
folate = 1.91 nmol/L) (95% CI -0.03 to 3.86 nmol/L) (P = 0.05). Further, we found strong and significant positive interactions between the MTHFR 1793G>A and 1298A>C mutations on vitamin B12 concentrations.
Conclusion
Higher folate concentrations in kidney transplant recipients with MTHFR 1793GA or 1793AA and markedly higher concentrations of vitamin B12 in patients with combined MTHFR 1793G>A and 1298A>C mutations may contribute to the survival advantage that has been postulated for such patients showing these genotypes.
Keywords:
MTHFR, genetic polymorphism, mutation, vitamin B12, folate, homocysteine, kidney transplants
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