Homocysteine levels -before and after methionine loading- in 51 Dutch families

M. den Heijer, S. Graafsma, S.Y. Lee, P. Verhoef

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

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
Pages (from-to)753-762
JournalEuropean Journal of Human Genetics
Volume13
Issue number6
DOIs
Publication statusPublished - 2005

Keywords

  • cardiovascular-disease
  • vascular-disease
  • heart-disease
  • risk-factor
  • plasma
  • hyperhomocysteinemia
  • metaanalysis
  • prevalence
  • variability
  • thrombosis

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