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

Authors
den Heijer, M; Graafsma, S; Lee, SY; van Landeghem, B; Kluijtmans, L; Verhoef, P; Beaty, TH; Blom, H
Citation
European journal of human genetics : EJHG, 13(6):753-762, 2005
Journal Title
European journal of human genetics : EJHG
ISSN
1018-48131476-5438
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.
MeSH terms
AdultFemaleGenotypeHomocysteine/blood*HumansInheritance Patterns*MaleMethionine/metabolism*Methylenetetrahydrofolate Reductase (NADPH2)/genetics*Middle AgedModels, GeneticNetherlandsPedigreePolymorphism, GeneticRegression AnalysisRisk Factors
DOI
10.1038/sj.ejhg.5201389
PMID
15756298
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Preventive Medicine & Public Health
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