Clinical Chemistry
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Clinical Chemistry 53: 971-979, 2007. First published April 5, 2007; 10.1373/clinchem.2006.082149
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
clinchem.2006.082149v1
53/5/971    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (8)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bathum, L.
Right arrow Articles by Kyvik, K. O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bathum, L.
Right arrow Articles by Kyvik, K. O.
Related Collections
Right arrow Molecular Diagnostics and Genetics
Right arrow Nutrition
Right arrow Other Areas of Clinical Chemistry
Right arrow Hemostasis and Thrombosis
Right arrow Hematology
Right arrow Endocrinology and Metabolism
(Clinical Chemistry. 2007;53:971-979.)
© 2007 American Association for Clinical Chemistry, Inc.

Other Areas of Clinical Chemistry

Genetic and Environmental Influences on Plasma Homocysteine: Results from a Danish Twin Study

Lise Bathum1,2,a, Inge Petersen2, Lene Christiansen1,2, Agnieszka Konieczna1, Thorkild I.A. Sørensen3 and Kirsten O. Kyvik2

1 Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Odense, Denmark.
2 Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
3 Institute of Preventive Medicine, Copenhagen University Hospital, Centre for Health and Society, Copenhagen, Denmark.

aAddress correspondence to this author at: Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Soendre Boulevard 29, DK-5.000 Odense C, Denmark. Fax 45-6541-1911. e-mail: lisebathum{at}dadlnet.dk.

Background: Increased plasma homocysteine has been linked to many clinical conditions including atherosclerosis and ischemic stroke. We assessed the genetic and environmental influences on homocysteine in adult twins and tested the influence of 3 candidate polymorphisms.

Methods: Homocysteine was analyzed in 1206 healthy twins, who were genotyped for 3 polymorphisms: MTHFR 677C>T, MTR 2756A>G, and NNMT (dbSNP: rs694539). To perform quantitative trait linkage analysis of the MTHFR locus, the genotyping was supplemented with 2 genetic markers localized on each site of the MTHFR locus. The twin data were analyzed using biometric structural equation models as well as a combined association and linkage analysis in 2 age cohorts.

Results: Age, sex, and MTHFR genotype have a significant impact on homocysteine concentrations, whereas the other genotypes were not associated with homocysteine concentrations. The variance in homocysteine could be solely ascribed to additive genetic and nonshared environmental factors, with an estimated additive genetic proportion of total variation at age 18–39 years of 0.63 (95% CI, 0.53–0.71) and at age 40–65 years of 0.27 (95% CI, 0.10–0.41). The impact of the MTHFR locus is estimated to explain 53% (95% CI, 0.07–0.67) of the total phenotypic variation in persons 18–39 years old and 24% (95% CI, 0.00–0.39) in persons 40–65 years old, i.e., almost all additive genetic variance.

Conclusions: Homocysteine concentrations have a high heritability that decreases with age. The MTHFR gene locus is responsible for almost all the variation attributable to genetic factors, leaving very little influence of other genetic variations.




The following articles in journals at HighWire Press have cited this article:


Home page
 Clin. Chem.Home page
D. I. Chasman, G. Pare, and P. M Ridker
Population-Based Genomewide Genetic Analysis of Common Clinical Chemistry Analytes
Clin. Chem., January 1, 2009; 55(1): 39 - 51.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
L. M.J.W. van Driel, H. P.M. Smedts, W. A. Helbing, A. Isaacs, J. Lindemans, A. G. Uitterlinden, C. M. van Duijn, J. H.M. de Vries, E. A.P. Steegers, and R. P.M. Steegers-Theunissen
Eight-fold increased risk for congenital heart defects in children carrying the nicotinamide N-methyltransferase polymorphism and exposed to medicines and low nicotinamide
Eur. Heart J., June 1, 2008; 29(11): 1424 - 1431.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
P. M. Ueland and R. Clarke
Homocysteine and Cardiovascular Risk: Considering the Evidence in the Context of Study Design, Folate Fortification, and Statistical Power
Clin. Chem., May 1, 2007; 53(5): 807 - 809.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the American Association for Clinical Chemistry.