Homocysteine levels - Before and after methionine loading - In 51 Dutch families

Martin den Heijer, Sietze Graafsma, Soon Young Lee, Bart van Landeghem, Leo Kluijtmans, Petra Verhoef, Terri L Beaty, Henk Blom

Research output: Contribution to journalArticle

Abstract

Elevated levels of homocysteine are a risk factor for vascular disease, thrombosis, neural tube defects and dementia. The 677C > T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene appears to be the most important single determinant of plasma homocysteine concentration. In the current study, we estimated heritability and fit a series of models of inheritance for both fasting and postmethionine-load homocysteine levels in the HOFAM-study (HOmocysteine in FAMilies study), which included 306 participants from 51 pedigrees, ascertained through a hyperhomocysteinemic proband. The crude heritability was 21.6% for fasting and 67.5% for postloading homocysteine. After adjustment for MTHFR 677C > T genotype, heritability dropped to 5.2 and 63.9%, respectively. Segregation analysis revealed that a nongenetic model with equal transmission was the best fitting and most parsimonious model for fasting homocysteine levels, while a two-distribution, Mendelian model with residual familial correlation was best for postmethionine-load homocysteine levels. This study shows that postload homocysteine levels have a stronger genetic determination than do fasting homocysteine levels. The heritability of postload homocysteine levels were not strongly affected by adjustment for MTHFR 677C > T genotype, in contrast to fasting homocysteine levels. Further studies are needed to identify the genes responsible for the inheritance of postload homocysteine levels.

Original languageEnglish (US)
Pages (from-to)753-762
Number of pages10
JournalEuropean Journal of Human Genetics
Volume13
Issue number6
DOIs
StatePublished - Jun 2005

Fingerprint

Homocysteine
Methionine
Fasting
Methylenetetrahydrofolate Reductase (NADPH2)
Genotype
Neural Tube Defects
Pedigree
Vascular Diseases
Genes
Dementia
Thrombosis

Keywords

  • B-vitamins
  • Heritability
  • Homocysteine
  • Methionine loading test
  • MTHFR
  • Segregation analysis

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

den Heijer, M., Graafsma, S., Lee, S. Y., van Landeghem, B., Kluijtmans, L., Verhoef, P., ... Blom, H. (2005). Homocysteine levels - Before and after methionine loading - In 51 Dutch families. European Journal of Human Genetics, 13(6), 753-762. https://doi.org/10.1038/sj.ejhg.5201389

Homocysteine levels - Before and after methionine loading - In 51 Dutch families. / den Heijer, Martin; Graafsma, Sietze; Lee, Soon Young; van Landeghem, Bart; Kluijtmans, Leo; Verhoef, Petra; Beaty, Terri L; Blom, Henk.

In: European Journal of Human Genetics, Vol. 13, No. 6, 06.2005, p. 753-762.

Research output: Contribution to journalArticle

den Heijer, M, Graafsma, S, Lee, SY, van Landeghem, B, Kluijtmans, L, Verhoef, P, Beaty, TL & Blom, H 2005, 'Homocysteine levels - Before and after methionine loading - In 51 Dutch families', European Journal of Human Genetics, vol. 13, no. 6, pp. 753-762. https://doi.org/10.1038/sj.ejhg.5201389
den Heijer M, Graafsma S, Lee SY, van Landeghem B, Kluijtmans L, Verhoef P et al. Homocysteine levels - Before and after methionine loading - In 51 Dutch families. European Journal of Human Genetics. 2005 Jun;13(6):753-762. https://doi.org/10.1038/sj.ejhg.5201389
den Heijer, Martin ; Graafsma, Sietze ; Lee, Soon Young ; van Landeghem, Bart ; Kluijtmans, Leo ; Verhoef, Petra ; Beaty, Terri L ; Blom, Henk. / Homocysteine levels - Before and after methionine loading - In 51 Dutch families. In: European Journal of Human Genetics. 2005 ; Vol. 13, No. 6. pp. 753-762.
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