Influence of genetic variants of IDH1, IDH2, TET2 and DNMT3A on cytarabine cytotoxicity in different populations

This study is aimed to explore the association between influence of genetic variants of IDH1, IDH2, TET2 and DNMT3A on cytarabine cytotoxicity in European and/or African populations. MethodsHapMap cell lines derived from European descent (CEU) and African descent (YRI) were exposed to ara‐C at different concentrations (1, 5, 40 and 80 μmol/L). The per cent survival values at each concentration were determined after 72‐hour exposure to ara‐C. The area under the survival curve (AUC) was calculated using the trapezoidal rule, and AUC values were log2‐transformed before statistical analysis. The 15 tagged single nucleotide polymorphism (SNPs) (rs2970357 and rs2970359 of IDH2, rs2242234 and rs1044147 of TET2, rs12999687 and rs6739187 of DNMT3A from CEU subjects, rs8040937 and rs1506941 of IDH2, rs6819857, rs7661962, rs7377314, rs6811804, rs4690309, rs4076064, rs6823876 of TET2 from YRI subjects) were selected utilizing Haploview. Minor allele frequency was more than 5% of them. Minimum pairwise r2 was at least .80, and the correlation between genetic polymorphisms within IDH1, IDH2, TET2 and DNMT3A and AUC of ara‐C was assessed. Results and discussionThe genotypes of 2 SNPs in IDH2 including synonymous SNP located at 3′ UTR and 2 intrinsic SNPs in DNMT3A were significantly associated with ara‐C sensitivity depicted by lower AUC in European ancestry; however, no one in DNMT3A was significant in African ancestry. Most interestingly, there was no one genotype of SNP...
Source: Journal of Clinical Pharmacy and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research