1. ¹Department of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
2. ²General Clinical Research Center, Medical University of South Carolina, Charleston, SC, USA
3. ³Vitamin Metabolism Laboratory, Jean Mayer-USDA Human Nutrition Center on Aging at Tufts University, Boston, MA, USA
4. ⁴Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Center on Aging at Tufts University, Boston, MA, USA

Correspondence: Dr HJ Blom, Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel: +31 24 3613469; Fax: +31 24 3618900; E-mail: H.Blom@cukz.umcn.nl

Received 24 January 2005; Revised 4 May 2006; Accepted 16 May 2006; Published online 21 June 2006.

Abstract

Elevated total plasma homocysteine concentrations (tHcy), both fasting and post-methionine load, have been established as risk factors for vascular disease. Recently, we described the association of a 31 bp variable number of tandem repeats (VNTR) in the cystathionine -synthase (CBS) gene with both CBS enzyme activity and tHcy concentrations. In the present study, we determined the 31 bp VNTR genotypes in 2598 individuals of the Framingham Offspring Study and studied the association between this genotype and fasting, 2-h post-methionine load and delta (ie increase upon methionine loading) tHcy concentrations in 1416 subjects. We observed a positive association between the number of repeat units of the CBS 31 bp VNTR and both postload and delta tHcy concentrations. Adjustment for possible effect modifying factors like age, sex and vitamin (B₆, B₁₂ and folate) status did not change this observation. We hereby confirm the results of our earlier study, in which we found that this 31 bp VNTR is a genetic determinant of post-methionine load tHcy concentrations. Since also post-methionine load tHcy concentrations are found to be associated with an increased risk for cardiovascular disease (CVD), this 31 bp VNTR may be considered a risk factor for CVD.