RESUMO
BACKGROUND: Drug degradation in the human organism is driven by detoxification mechanisms that can be affected in their efficiency by genetic mutations. The purpose of this pilot investigation was to investigate whether Type 2 diabetes is associated with mutations in prominent members of the CYP 450 isoenzyme family. METHODS: Genomic DNA was isolated from EDTA blood samples of 203 Caucasian subjects (101 patients with Type 2 diabetes and 102 non-diabetic subjects, age (mean +/- STD): 49 +/- 16 years) was analyzed. Genomic DNA was isolated from EDTA blood. Mutation analysis for CYP2C8 (*2/*3/*4), CYP2C9 (*2/*3), CYP2C19 (*2/*3), CYP2D6 (*3/*4/*5/*6) and PPARgamma (P12A) was performed by means of real-time PCR methods (Light-Cycler, Roche Diagnostics, Indianapolis, IN, USA). RESULTS: The genotyping revealed the following allele frequency distributions for the two investigated groups: CYP2C8: *2 (type 2 diabetes 3% vs. 1%, n.s.), *3 (16% vs. 3%, n.s.), *4 (15% vs. 2%, p < 0.05), CYP2C9: *2 (20% vs. 24%, n.s.), *3 (22% vs. 21%, n.s.), CYP2C19: *2 (23% s. 33%, n.s.), *3 (0% vs. 0%, n.s.), CYP2D6: *3 (3% vs. 4%, n.s.), *4 (40% vs. 37%, n.s.), *5 (3% vs. 2%, n.s.), *6 (0% vs. 0%, n.s.), PPARgamma P12A (15% vs. 21%, n.s.), i.e. all but one mutation (CYP2C8*4) were found with equal prevalence in the two cohorts. CONCLUSIONS: In this pilot investigation, we found an increased prevalence of the CYP2C8*4 mutation in the Type 2 diabetic patient group. This may result in a modification of drug degradation and drug efficacy in these patients and may have an influence, e.g. on the choice of anti-diabetic drugs. However, further trials are necessary in order to confirm our findings.
