1. ¹Laboratory of Pediatrics and Neurology, University Medical Center Nijmegen, The Netherlands
2. ²Department of Internal Medicine, University Medical Center Nijmegen, The Netherlands
3. ³Department of Internal Medicine, Division of Endocrinology, University Medical Center Nijmegen, The Netherlands
4. ⁴Wageningen Center for Food Sciences and Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, The Netherlands

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

Received 4 June 2002; Revised 7 August 2002; Accepted 26 August 2002.

Abstract

Hyperhomocysteinaemia is generally accepted as an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. The only way of homocysteine degradation is conversion to cysteine in the transsulfuration pathway in which the regulating step is catalysed by cystathionine -synthase (CBS). Mild impairment of CBS function could therefore affect homocysteine concentration, in particular after methionine loading, and consequently cardiovascular disease (CVD) risk. We analysed two silent polymorphisms and one short tandem repeat in the CBS gene (ie 699CT, 1080CT and –5697 (GT) STR) as genetic markers potentially in linkage disequilibrium with a functional polymorphism. We assessed their association with fasting and post-methionine load homocysteine in 190 patients with arterial occlusive disease, and in 381 controls. No differences in CBS genotype frequencies between cases and controls were found, nor was a particular CBS genotype associated with an elevated risk of arterial occlusive disease. Although we did find a high rate of linkage disequilibrium between the two single nucleotide polymorphisms and the GT STR, none of the genotypes defined by the three CBS variants studied showed an association with elevated fasting, post-load or increase upon methionine loading homocysteine concentrations. In conclusion, we did not find any indication that genetic variation in the CBS gene is associated with increased homocysteine concentrations.