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- Title
Homocysteine levels-before and after methionine loading-in 51 Dutch families.
- Authors
den Heijer, Martin; Graafsma, Sietze; Soon Young Lee; Van Landeghem, Bart; Kluijtmans, Leo; Verhoef, Petra; Beaty, Terri H; Blom, Henk
- 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.European Journal of Human Genetics (2005) 13, 753-762. doi:10.1038/sj.ejhg.5201389 Published online 9 March 2005
- Subjects
HOMOCYSTEINE; GENETIC polymorphisms; VASCULAR diseases; HUNTINGTON disease; PROTEIN S deficiency; HUMAN biology
- Publication
European Journal of Human Genetics, 2005, Vol 13, Issue 6, p753
- ISSN
1018-4813
- Publication type
Article
- DOI
10.1038/sj.ejhg.5201389