title: Homocysteine levels--before and after methionine loading--in 51 Dutch families.
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.
authors.affiliation: Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. M.denHeijer@endo.umcn.nl
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.forename: Sietze
authors.initials: S
authors.lastname: Graafsma
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Bart
authors.initials: B
authors.lastname: van Landeghem
authors.forename: Leo
authors.initials: L
authors.lastname: Kluijtmans
authors.forename: Petra
authors.initials: P
authors.lastname: Verhoef
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.forename: Henk
authors.initials: H
authors.lastname: Blom
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008715:Methionine / Q000378:metabolism*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D009426:Netherlands; D010375:Pedigree; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)