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J Am Soc Nephrol 11:1918-1925, 2000
© 2000 American Society of Nephrology

Effect of MTHFR 1298A->C and MTHFR 677C->T Genotypes on Total Homocysteine, Folate, and Vitamin B12 Plasma Concentrations in Kdiney Graft Recipients

MANUELA FÖDINGER*, HEIDI BUCHMAYER*, GOTFRIED HEINZ{dagger}, MENELAOS PAPAGIANNOPOULOS*, JOSEF KLETZMAYR{ddagger}, SUSANNE RASOUL-ROCKENSCHAUB§, WALTER H. HÖRL{ddagger} and GERE SUNDER-PLASSMANN{ddagger}

* Department of Laboratory Medicine, Division of Molecular Biology, University of Vienna, Austria.
{dagger} Department of Medicine II, Division of Cardiology and Angiology, University of Vienna, Austria.
{ddagger} Department of Medicine III, Division of Nephrology and Dialysis, University of Vienna, Austria.
§ Department of Surgery, Division of Transplant Surgery, University of Vienna, Austria.

Correspondence to Dr. Gere Sunder-Plassmann, Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin III, A-1090 Wien, Währinger Gürtel 18-20, Austria. Phone: +43-1-40400-4391; Fax: +43-1-40400-4392; E-mail: Gere.Sunder-Plassmann{at}akh-wien.ac.at

Abstract. The effect of 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C->T and 1298A->C on total homocysteine (tHcy), folate and vitamin B12 levels was investigated in 733 kidney graft recipients. The six major genotype combinations were used as grouping variables, and age, gender, BMI, serum creatinine, and creatinine clearance and ln-folate, ln-vitamin B12, or logarithmus naturalis tHcy (ln-tHcy) were used as covariates in three ANCOVA and multiple stepwise linear regression models. Hyperhomocysteinemia was present in 49.7% of the patients. The allele frequency of MTHFR 677T and 1298C was 0.319 and 0.326. MTHFR genotype and all other variables were significant predictors of ln-tHcy (higher tHcy plasma levels for MTHFR 677TT/1298AA versus all other five genotype groups: P < 0.05). BMI, creatinine clearance, ln-tHcy, and MTHFR genotype influenced ln-folate (lower folate levels for MTHFR 677TT/1298AA versus all other genotype groups: P < 0.05). Creatinine clearance and ln-tHcy were the only predictors of ln-vitamin B12 levels. In a prespecified subgroup analysis (n = 496), the MTHFR genotype also influenced tHcy levels and compound heterozygous patients had significantly lower folate levels as compared with MTHFR 677CC/1298AA and 677CC/1298CC. This study shows that the MTHFR 677TT/1298AA and 677CT/1298AC genotypes are significant predictors of tHcy and folate plasma levels.




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