title: NAMPT and NAPRT1: novel polymorphisms and distribution of variants between normal tissues and tumor samples.
abstract: Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase domain containing 1 (NAPRT1) are the main human NAD salvage enzymes. NAD regulates energy metabolism and cell signaling, and the enzymes that control NAD availability are linked to pathologies such as cancer and neurodegeneration. Here, we have screened normal and tumor samples from different tissues and populations of origin for mutations in human NAMPT and NAPRT1, and evaluated their potential pathogenicity. We have identified several novel polymorphisms and showed that NAPRT1 has a greater genetic diversity than NAMPT, where any alteration can have a greater functional impact. Some variants presented different frequencies between normal and tumor samples that were most likely related to their population of origin. The novel mutations described that affect protein structure or expression levels can be functionally relevant and should be considered in a disease context. Particularly, mutations that decrease NAPRT1 expression can predict the usefulness of Nicotinic Acid in tumor treatments with NAMPT inhibitors.
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Duarte-Pereira
authors.affiliation: IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Silva
authors.affiliation: 1] IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal [2] Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Azevedo
authors.affiliation: IEETA - Institute of Electronics and Telematics Engineering of Aveiro, University of Aveiro, Santiago Campus, 3810-193 Aveiro, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Castro
authors.affiliation: 1] IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal [2] Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Amorim
authors.affiliation: 1] IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal [2] IEETA - Institute of Electronics and Telematics Engineering of Aveiro, University of Aveiro, Santiago Campus, 3810-193 Aveiro, Portugal.
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Silva
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D009243:NAD / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics*; D010430:Pentosyltransferases / Q000096:biosynthesis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
chemical_list: D016207:Cytokines; D009243:NAD; D010430:Pentosyltransferases; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; C021864:nicotinate phosphoribosyltransferase