The CYP2C9 gene is related to the metabolism of several non-steroidal antiinflammatory drugs (NSAID). Presence of different allele polymorphisms is associated with lack of enzyme activity and can lead to therapeutic failure. The aim of our study was to provide data about the distribution of CYP2C9 alleles in voluntary donors from the Macedonian Bone Marrow Donor Registry (MBMDR) and to calculate the activation score (AS) of CYP2C9 enzyme.We analyzed samples of 25 voluntary bone marrow donors by multiplex real-time polymerase chain reaction (PCR) test for detection of CYP2C9*2 and *3 polymorphisms. The samples were analyzed with 7500 Real-Time PCR System with FAM, VIC, ROX and Cy5 filters.We identified 13 donors with *1*1 diplotype, 7 with *1*3 diplotype, 4 with *1*2 diplotype and 1 donor with *2*3 diplotype. According to the calculated AS, 13 out of 25 individuals (54%) had normal AS value of 2, which refers to normal metabolizers (NMs). Eleven donors (44%) had AS value of 1-1.5, which refers to intermediate metabolizers (IMs) and only one donor (4%) had AS value of 0.5 which refers to poor metabolizer (PM).Even though the number of donors in our study is small and the results need to be evaluated in a larger cohort, it shows that different genotypes in the CYP2C9 gene are present among donors from MBMR. It is important to have it in mind especially when using NSAIDs that can be bought over-the-counter.
Clopidogrel has an antiplatelet effect, which is used to reduce the risk of myocardial infarction and stroke in high-risk patients in the context of primary prophylaxis. In the body it is subjected to metabolism by the liver enzyme system CYP450.In this project, laboratory conditions have been established to determine the polymorphisms of the CYP450 2C19 gene.The structure of the polymorphisms in the CYP450 2C19 gene and the type of metabolizer has been determined.This study included 42 heart patients with St. post PCI, mean age 65-9.7 years, treated with 75 mg Clopidogrel daily.The following polymorphisms were examined: c.681G> A; c.636G> A; c.1A> G; c.1297C> T; c.395G> A; c.819 + 2T> A; c.358T> C; c.-806C> T.Appropriate laboratory conditions have been established for the precise determination of polymorphisms in the CYP450 2C19 gene and the determination of the type of metabolizer.The results showed that in our patients the largest number of polymorphisms occur at the position c.681G> A which leads to the creation of an intermediate metabolizer, while the polymorphism at the position c.-806C> T leads to the creation of an ultrafast metabolite.The largest number of polymorphisms occurs in c.681G> A CYP450 2C19 gene, which leads to the creation of an intermediate metabolizer.Because of this, and before starting the therapy in patients St. post PCI, it is necessary to first determine what clopidogrel metabolizers they are and whether they possess LF or GF alleles.
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