title: Genetic polymorphisms of CYP3A4, GSTT1, GSTM1, GSTP1 and NQO1 and the risk of acquired idiopathic aplastic anemia in Caucasian patients.
abstract: OBJECTIVE
  Various drugs and xenobiotics are involved in the pathogenesis of acquired aplastic anemia. Their harmful potential depends on the amount of exposure to them and on the detoxifying capacity of the recipient. Genetic polymorphisms of some important detoxifying enzymes are associated with low or absent cata-lytic activity of the protein. We assessed whether, in a Caucasian population, low or null activity polymorphisms of CYP3A4, GSTT1, GSTM1, GSTP1 and NQO1 were associated with the risk of developing aplastic anemia and with the response to immunosuppressive therapy.
  
  
  METHODS
  In 77 Caucasian patients with aplastic anemia and in 156 normal controls we evaluated the distribution of the following polymorphisms which are associated with low or no activity of the corresponding enzyme: (i)-290 A-->G of the CYP3A4 gene, deletions of (ii) GSTT1 and (iii) GSTM1 genes, (iv) 313A-->G of the GSTP1 gene and (v) 609 C-->T of the NQO1 gene.
  
  
  RESULTS
  The distribution of the genotypes of all tested polymorphisms was not different in patients and controls. No differences were seen among the patients when the group was subdivided by age and severity of the disease. Only the GSTM1 null genotype was significantly more frequent in male patients than in male controls. The frequency of all tested polymorphisms did not differ in patients who did or did not respond to immunosuppressive therapy.
  
  
  CONCLUSIONS
  The low/null activity polymorphisms of the detoxifying enzymes CYP3A4, GSTT1, GSTM1, GSTP1 and NQO1 are not associated with the risk of developing aplastic anemia or to the response to immunosuppressive therapy in Caucasian patients.
authors.affiliation: Hematology Unit, Department of Pediatric Hemato-Oncology, Giannina Gaslini Children's Hospital, Genoa, Italy. carlodufour@ospedale-gaslini.ge.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.forename: Johanna
authors.initials: J
authors.lastname: Svahn
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: Daniela
authors.initials: D
authors.lastname: Longoni
authors.forename: Stefania
authors.initials: S
authors.lastname: Varotto
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Iori
authors.forename: Francesca
authors.initials: F
authors.lastname: Bagnasco
authors.forename: Anna
authors.initials: A
authors.lastname: Locasciulli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Menna
authors.forename: Ugo
authors.initials: U
authors.lastname: Ramenghi
authors.forename: Marina
authors.initials: M
authors.lastname: Lanciotti
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011110:Polymorphism, Genetic; D012016:Reference Values; D044465:White People / Q000235:genetics
chemical_list: D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); C510163:CYP3A4 protein, human; C447479:NQO1 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human