Analysis of carrying clinically significant allelic variants of TPMT and DPYD genes associated with the response to drug therapy in cancer practice among 9 ethnic groups of the Russian Federation

Abstract

Aim. To study the peculiarities of carrying clinically significant allelic variants of TPMT and DPYD genes associated with the response to drug therapy in cancer practice among 9 ethnic groups of the Russian Federation. Materials and methods. The study included 1446 conditionally healthy volunteers from 9 ethnic groups. Carriage of polymorphic TPMT and DPYD gene markers was detected by the Real-Time PCR (polymerase chain reaction) method. Results. In all ethnic groups, the distribution of genotypes and alleles matched the equilibrium of Hardy-Weinberg. TPMT*3A (rs1800460) and TPMT*3C (rs1142345) were observed in heterozygous state in all investigated ethnic groups. In the Kabardinian group (n=204) the frequency of the TPMT*3A minor allele (MAF, %) was 2.94%; Balkars (n=200) 1.25%; Ossetians (n=239) 1.67%; Chuvashes (n=238) 1.89%: Mari (n=206) 1.21%; Tatars (n=141) 1.77%; Russians (n=134) 4.85%. The frequency of the TPMT*3C minor allele (MAF, %) in the Kabardinian group (n=204) MAF was 4.90%; Balkars (n=200) 1. 75%; Buryats (n=114) 0.44%; Ossetians (n=239) 1.88%; Chuvashes (n=238) 1.68%: Mari (n=206) 1.21%; Tatars (n=141) 1.42%; Russians (n=134) 4.48%. The results of the analysis of DPYD*2A polymorphism (rs3918290) demonstrated ethnic peculiarities of distribution. In the heterozygous state it was found only in the groups of Kabardins (n=204, MAF 1.22%), Balkars (n=200, MAF 2.00%), and Ossetians (n=239, MAF 0.63%). Conclusion. The results obtained in the study will be useful for developing personalized algorithms of antitumor therapy in cancer practice, including those aimed at increasing the safety of chemotherapy.

Keywords

• pharmacogenetic
• chemotherapy
• ethnic groups
• tpmt
• dpyd