Genetic polymorphisms of CYP3A4, GSTT1, GSTM1, GSTP1 and NQO1 and the risk of acquired idiopathic aplastic anemia in Caucasian patients

Abstract

Background and objectives: 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.

Design and 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.

Interpretation and 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.