Homocysteine levels - Before and after methionine loading - In 51 Dutch families
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.... Mehr ...
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Dokumenttyp: | Artikel |
Erscheinungsdatum: | 2005 |
Reihe/Periodikum: | den Heijer , M , Graafsma , S , Lee , S Y , van Landeghem , B , Kluijtmans , L , Verhoef , P , Beaty , T H & 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 |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-27076843 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | https://research.vumc.nl/en/publications/f6077864-8dd6-42b2-8e7c-0565b65e280c |
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.