FREQUENCIES OF POLYMORPHISMS IN THE CYTOCHROME’S P450 GENES OF WARFARIN TRANSFORMATION IN A EUROPEAN POPULATION OF EASTERN SIBERIA
Частоты полиморфизмов генов цитохрома P450, участвующих в метаболизме варфарина, в европейской популяции Восточной Сибири
2018-09-28
SCID: 54.1/8dh9zkyq
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CYP2C9 polymorphismsCYP4F2 1347 C>TEastern Siberian Caucasiansreal-time PCRwarfarin pharmacogenetics
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Abstract (AI)
Background. Genotypes of the cytochrome p450 isoform (CYP2C9 and CYP4F2) determine warfarin dose requirements. Frequencies of risk alleles and genotypes of CYP2C9 and CYP4F2 gene vary in different races and ethnic groups. Aim. This study analyzed the frequencies of *2, *3 alleles of CYP2C9 gene and the 1347 C>T allele of CYP4F2 gene in the Caucasians of Eastern Siberia, and compare with other populations. Materials and methods. Participants were 147 patients (Caucasians): 67 (45.58 %) man and 80 (54.42 %) women), taking warfarin for the prevention of thrombosis with a mean age of 64.74 ± 14.29 years. There were patients with atrial fibrillation – 77 (52.38 %) persons, coronary artery disease – 10 (6.80 %), pulmonary embolism – 5 (3.40 %), 15 (10.20 %) patients after implantation of an mechanical heart valve, etc. The subjects were genotyped for CYP2C9 (*1,*2,*3), and CYP4F2 (1347 C>T) by real-time polymerase chain reaction (RT-PCR) using “Pharmacogenetics Warfarin” reagent kits (DNA technology, Russia). Results. 69.4 % of Caucasians of Eastern Siberia (Russians), have two functional alleles (*1/*1) of CYP2C9 (they’re extensive/normal metabolizers), the number of intermediate metabolizers (*1/*2, *1/*3) was 29.8 % and 0.68 % of slow metabolizers (*3/*3). Homozygous carriers of two non-functional alleles *2 and *3 (*2/*2, *2/*3) were absent. Carriers of one coumarin-resistant Т-allele of CYP4F2 were 57 (38.7 %) respondents, two coumarin-resistant alleles – 10 (6.8 %) respondents. Conclusions. Frequencies of polymorphisms in the Cytochrome’s p450 genes of warfarin transformation in a European population of Eastern Siberia have no differences with other European populations of the world
Key Findings
1
A CYP4F2 coumarin-resistant T allele was present in 38.7% of participants heterozygously and 6.8% homozygously.
2
CYP2C9 *1/*1, indicating normal metabolism, occurred in 69.4% of participants; intermediate-metabolizer genotypes occurred in 29.8%.
3
Only 0.68% of participants carried the CYP2C9 *3/*3 slow-metabolizer genotype, while *2/*2 and *2/*3 genotypes were absent.
4
The observed CYP2C9 and CYP4F2 polymorphism frequencies did not differ from those reported in other European populations.
5
The study characterized CYP2C9 (*2, *3) and CYP4F2 1347 C>T polymorphism frequencies among 147 Caucasian warfarin-treated patients from Eastern Siberia.
Research Object
CYP2C9 and CYP4F2 genes in warfarin-treated Caucasian patients from Eastern Siberia
Research Subject
Frequencies and distribution of warfarin-relevant polymorphisms and metabolizer genotypes in CYP2C9 and CYP4F2
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2018-09-28
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