1Division of Clinical Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping, Sweden; 2Division of Molecular Genetic Diagnostics, Department of Clinical Biochemistry, University of Copenhagen, Copenhagen, Denmark; 3The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; 4Department of Clinical Pharmacology, Bispebjerg Hospital, Copenhagen, Denmark; 5Department ...

Mutations in BRCA1 and BRCA2 genes may cause defective DNA repair and increase the risk for breast cancer. Folate deficiency is associated with increased breast cancer risk and induces chromosome abnormalities. We hypothesized that BRCA1 and BRCA2 germline mutation carriers are more sensitive to the genome damaging effect of folate deficiency compared with healthy non-carrier controls and that ...

Individuals with Down syndrome (DS) present decreased homocysteine (Hcy) concentration, reflecting a functional folate deficiency secondary to overexpression of the cystathionine ss-synthase gene. Since plasma Hcy may be influenced by genetic polymorphisms, we evaluated the influence of C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR), of A2756G polymorphis...

The reduced folate carrier (RFC) protein has a secondary structure consistent with the predicted 12 transmembrane (TM) domains, intracellular N- and C-termini and a large cytoplasmic loop between TM6 and TM7. In the present study, the role of the cytoplasmic domains in substrate transport and protein biogenesis were examined using an array of hamster RFC deletion mutants fused to enhanced green...

Over the past 10 years, animal studies have uncovered the molecular mechanisms for the renal tubular recovery of filtered vitamin and vitamin carrier proteins. Relatively few endocytic receptors are responsible for the proximal tubule uptake of a number of different vitamins, preventing urinary losses. In addition to vitamin conservation, tubular uptake by endocytosis is important to vitamin me...