title: In silico search for single nucleotide polymorphisms in genes important in vitamin E homeostasis.
abstract: Large inter-individual variation exists in the response to vitamin E supplementation, and this may influence the outcome of human studies. It is our hypothesis that genetic heterogeneity is an important determinant of vitamin E homeostasis. Therefore we have performed an in silico search for single nucleotide polymorphisms (SNPs) associated with genes involved in vitamin E homeostasis. Based on function, the following genes were considered as candidates for vitamin E heterogeneity: c-tocopherol transfer protein (TTPA), tocopherol associated protein (TAP), lipoprotein lipase (LPL), multidrug resistance protein 2 (MDR-2), pregnane X receptor (PXR) and members of the cytochrome P450 family (CYP). Searches for coding SNPs were initiated from web based programs of the National Center for Biotechnology Information (NCBI). SNP frequencies were calculated by dividing the number of annotated coding SNPs by the number of base pairs in the open reading frame. Genes for TTPA, TAP and CYP3A5 had calculated SNP frequencies between 503 and 837 base pairs per coding SNP (bp/cSNP) and so are not highly polymorphic. In contrast, cSNP frequencies in LPL, MRP2, PXR, CYP3A4 and CYP4F2 were in the range of 100 bp/cSNP and so are highly polymorphic. Thus proteins involved in specific vitamin E binding are not highly polymorphic, may not influence inter-individual variation and so may not be good candidates for population studies. Proteins involved in drug/lipid metabolism which indirectly influence vitamin E status are highly polymorphic, are likely to influence inter-individual variation and so are good candidates for population studies. We suggest that future studies are aimed at addressing the role of such SNPs in vitamin E homeostasis.
authors.affiliation: Research Group-Molecular Nutrition, University of Kiel, Hermann-Weigmann-Street 1, 24103 Kiel, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Döring
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.forename: John K
authors.initials: JK
authors.lastname: Lodge
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D006706:Homeostasis; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics; D008954:Models, Biological; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D000077297:Pregnane X Receptor; D011485:Protein Binding; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics; D014810:Vitamin E / Q000235:genetics / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D000077297:Pregnane X Receptor; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; C017763:alpha-tocopherol transfer protein; D014810:Vitamin E; D003577:Cytochrome P-450 Enzyme System; C095122:multidrug resistance protein 3; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D000072470:Cytochrome P450 Family 4; C510163:CYP3A4 protein, human; C117480:CYP4F2 protein, human; D008071:Lipoprotein Lipase; D024502:alpha-Tocopherol