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Gen CYP2D6 spada u skupinu farmakogena koji sintetiziraju proteine uključene u apsorpciju, distribuciju, metabolizam i ekstrakciju (ADME) lijekova u organizmu. Ovaj gen smješten je na regiji 22q13.2, dugačak je 9,7 kb i kodira protein uključen u metabolizam antidepresiva, antipsihotika, neuroleptika, kao i lijekova koji sluţe za prevenciju kardiovaskularnih bolesti. U različitim se populacijama javljaju različite vrste genskih varijacija gena CYP2D6 s različitim učestalostima. Sekvenciranjem gena CYP2D6 na uzorku 323 hrvatskih Roma metodom sekvenciranja sljedeće generacije, kod 141 ispitanika otkrivene su nove mutacije. U ovom radu umnoţeni su dijelovi gena CYP2D6 prethodno okarakterizirani kao novootkrivene mutacije te je sekvenciranje ponovljeno Sangerovom metodom. PotvrĎena je mutacija na lokaciji chr22:42.129.127 (GRCh38) te je ustanovljena prevalencija od 0,159% u romskom uzorku. Preostale dvije mutacije nisu potvrĎene te je ustanovljena greška prilikom sekvenciranja metodom sljedeće generacije. Korištenjem softvera Protein Variant Effect Analyzer utvrĎeno je da se novootkrivena mutacija nalazi u protein-kodirajućoj regiji, no kako dovodi do sinonimne, odnosno tihe supstitucije, ovom promjenom nukleotida ne dolazi do zamjene aminokiseline odnosno do promjene strukture proteina. CYP2D6 gene belongs to a group of pharmacogens that synthesize proteins involved in the absorption, distribution, metabolism and extraction (ADME) of drugs. This 9.7 kb long gene is located in the 22q13.2 region and encodes the protein involved in the metabolism of antidepressants, antipsychotics, neuroleptics, and drugs used to prevent cardiovascular disease. Different populations show different genetic variants of the CYP2D6 gene with different frequencies. By sequencing the CYP2D6 gene on a sample of 323 Croatian Roma by next generation sequencing, new mutations were detected in 141 subjects. In this paper, the regions of the CYP2D6 gene in which new mutations were found, were amplified and sequencing was repeated by Sanger's method. Mutation was confirmed at location chr22:42.129.127 (GRCh38) with a prevalence of 0.159% in the Roma. Other two mutations were not confirmed, but an error that occurred during sequencing by the next generation method was established. Using the Protein Variant Effect Analyzer software, the newly discovered mutation is within the protein-coding region, but as a result of synonyms, ie silent substitution, this SNP does not result in the replacement of the amino acid or the change of the protein structure. |
