CONTEXT AND OBJECTIVE There is evidence that polymorphisms of genes involved in folate metabolism may be associated with higher risk that mothers may bear a Down's syndrome (DS) child. This study therefore had the objective of investigating the A80G polymorphism of the reduced folate carrier 1 (RFC1) gene and the C776G polymorphism of the transcobalamin 2 (TC2) gene as maternal risk factors for...

Leishmania donovani is the main cause of visceral leishmaniasis (VL) in East Africa. Differences between northern Ethiopia/Sudan (NE) and southern Ethiopia (SE) in ecology, vectors, and patient sensitivity to drug treatment have been described, however the relationship between differences in parasite genotype between these two foci and phenotype is unknown. Whole genomic sequencing (WGS) was ca...

BACKGROUND Evidence indicates RFC1 G80A polymorphism as a risk factor for a number of cancers. Increasing studies have been conducted on the association of RFC1 G80A polymorphism with acute lymphoblastic leukemia (ALL) risk. However, the results were controversial. The aim of the present study was to derive a more precise estimation of the relationship. MATERIALS AND METHOD PubMed, Embase, We...

Background We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymor...

Methods The data of 116 consecutive patients with JIA treated with MTX at the University Children’s Hospital Ljubljana from June 2011 to May 2014 have been retrospectively reviewed. The disease activity was measured by JADAS 71 score 3 and 6 months after the beginning of treatment with MTX and at the last follow up visit. All adverse events were noted separately for different organ systems. Gen...

•A variety of cancer cells rely on cytosolic 1C flux in physiological folate medium•Intracellular levels determine the versus mitochondrial flux•SLC19A1 regulates compartmentalized by modulating intracellular levels•SHMT1 is essential for growth low RFC-expressing tumors vitro and vivo Folate metabolism supplies one-carbon (1C) units biosynthesis methylation has long been a target chemotherapy....

ZD9331 is a drug that was developed from a potent class of water-soluble, C7-methyl-substituted, quinazoline-based inhibitors of thymidylate synthase (TS) that are transported into cells via a saturable, carrier-mediated system (reduced folate carrier, or RFC) but are not substrates for folylpolyglutamate synthetase. ZD9331 is the gamma-tetrazole analogue of 2-desamino-2, 7-dimethyl-N10-proparg...

RFC (reduced folate carrier) is the major transporter for reduced folates and antifolates [e.g. MTX (methotrexate)]. RFC is characterized by two halves, each with six TMD (transmembrane domain) alpha helices connected by a hydrophilic loop, and cytoplasmic N- and C-termini. We previously identified TMDs 4, 5, 7, 8, 10 and 11 as forming the hydrophilic cavity for translocation of (anti)folates. ...

BACKGROUND Impaired homocysteine metabolism is associated with a number of vasculopathies including extracranial aneurysms. We analyzed the possible association of nine genetic variants of homocysteine metabolism with the occurrence of intracranial aneurysms. METHODS Caucasian patients (n = 255) treated at two German hospitals for intracranial aneurysms and local controls (n = 348) were genot...

Folate deficiency during pregnancy has been related to low birth weight, preterm (PT) birth and other health risks in the offspring; however, it is unknown whether prematurity is related to low folate transport through the placenta due to altered expression of specific folate transporters. We determined placental expression (mRNA and protein concentrations by RT-qPCR and WB respectively) of spe...