Genetic polymorphisms of CYP3A4, GSTT1, GSTM1, GSTP1 and NQO1 and the risk of acquired idiopathic aplastic anemia in Caucasian patients.
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.
Dufour
Carlo
C
Hematology Unit, Department of Pediatric Hemato-Oncology, Giannina Gaslini Children's Hospital, Genoa, Italy. carlodufour@ospedale-gaslini.ge.it
Svahn
Johanna
J
Bacigalupo
Andrea
A
Longoni
Daniela
D
Varotto
Stefania
S
Iori
Anna Paola
AP
Bagnasco
Francesca
F
Locasciulli
Anna
A
Menna
Giuseppe
G
Ramenghi
Ugo
U
Lanciotti
Marina
M
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
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