EFFECT OF CYTOCHROME P450 2C9 GENE POLYMORPHISMS ON INDIVIDUAL SENSITIVITY TO GLICLAZIDE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Cytochrome P450 2C9, encoded by the gene CYP2C9 , is a key enzyme for the metabolism of most sulfonylurea (SU). It is known that the polymorphisms CYP2C9*2 and CYP2C9*3 are associated with decreased activity of cytochrome, which leads to an increase in plasma concentrations of SU and reduction in its clearance. The aim of the study was to assess the impact CYP2C9 polymorphisms on individual sensitivity to gliclazide in patients with type 2 diabetes. The study included 74 patients with newly diagnosed diabetes. For all patients gliclazide in a dose of 30 or 60 mg/day was prescribed. Dose titration was carried out for 6 months of observation. If necessary other glucose-lowering therapy (a combination of drugs or insulin) were prescribed. Following the results of study, all patients had achieved the target values of Hb A1c. In comparison with patients who had a polymorphic allele in the gene, patients with wild-type CYP2C9 had lower effective dose of gliclazide, more often required prescription of large (90-120 mg) doses of drug or other antihyperglycemic therapy. Conclusion: The presence of a polymorphic allele in the gene CYP2C9 in homo- or heterozygous state is associated with a decrease in the effective dose of gliclazide, used as monotherapy in patients with type 2 diabetes.