Agnes Weber1, Renata Szalai2, Csilla Sipeky3, Lili Magyari4, Marton Melegh5, Luca Jaromi6, Petra Matyas7, Balazs Duga8, Erzsebet Kovesdi9, Kinga Hadzsiev10, Bela Melegh11. 1. B.A.Z. County Hospital and University Teaching Hospital, Miskolc, Hungary. Electronic address: weber.onkorad@bazmkorhaz.hu. 2. Department of Medical Genetics, University of Pecs, Pecs, Hungary; Szentagothai Research Centre, University of Pecs, Pecs, Hungary. Electronic address: szalai.renata@pte.hu. 3. Department of Medical Genetics, University of Pecs, Pecs, Hungary; Szentagothai Research Centre, University of Pecs, Pecs, Hungary. Electronic address: sipeky.csilla@pte.hu. 4. Department of Medical Genetics, University of Pecs, Pecs, Hungary; Szentagothai Research Centre, University of Pecs, Pecs, Hungary. Electronic address: magyari.lili@pte.hu. 5. Department of Medical Genetics, University of Pecs, Pecs, Hungary. Electronic address: kioll@freemail.hu. 6. Department of Medical Genetics, University of Pecs, Pecs, Hungary; Szentagothai Research Centre, University of Pecs, Pecs, Hungary. Electronic address: jaromi.luca@pte.hu. 7. Department of Medical Genetics, University of Pecs, Pecs, Hungary. Electronic address: matyas.petra@pre.hu. 8. Department of Medical Genetics, University of Pecs, Pecs, Hungary; Szentagothai Research Centre, University of Pecs, Pecs, Hungary. Electronic address: duga.balazs@pte.hu. 9. Department of Medical Genetics, University of Pecs, Pecs, Hungary; Szentagothai Research Centre, University of Pecs, Pecs, Hungary. Electronic address: kovesdi.erzsebet@pte.hu. 10. Department of Medical Genetics, University of Pecs, Pecs, Hungary. Electronic address: hadzsiev.kinga@pte.hu. 11. Department of Medical Genetics, University of Pecs, Pecs, Hungary; Szentagothai Research Centre, University of Pecs, Pecs, Hungary. Electronic address: melegh.bela@pte.hu.
Abstract
BACKGROUND: Cytochrome P450 2B6 and 2D6 are important enzymes in human drug metabolism. These phase I enzymes are known to contribute the biotransformation of clinically important pharmaceuticals, including antidepressants, anticancer and anxiolytic drugs. The aim of this work was to determine the pharmacogenetic profile of CYP2B6 and CYP2D6 in Roma and Hungarian population samples. METHODS: A study population of 426 healthy Roma and 431 healthy Hungarian subjects were characterized for CYP2B6 c.516G>T, CYP2D6 c.100C>T and c.1846G>A polymorphisms using predesigned TaqMan Drug Metabolism Genotyping Real Time-PCR assays. RESULTS: We found significant differences in the presence of CYP2B6 c.516G>T (p<0.001), CYP2D6 c.100C>T (p=0.003) and c.1846G>A (p=0.022) between Hungarian and Roma population. The 516T allele frequency was 33.6% in the Roma group, 21.4% in Hungarians, whereas the minor CYP2D6 100T allele was present in 26.6% in Romas and 20.5% in Hungarians. The 1864A allele frequency was 22.5% in Roma and 18.1% in Hungarian samples. A significant increase was found in genotype frequencies for homozygous minor allele carrier Roma participants compared to Hungarians for CYP2B6 516TT and CYP2D6 100TT. The following CYP2D6 genotypes were identified in Roma samples: *1/*1 (55.4%), *1/*4 (2.1%), *1/*10 (3.1%), *4/*10 (38.7%), *10/*10 (0.7%). CONCLUSION: Our results demonstrate an increased minor allele frequency for CYP2B6 and CYP2D6 polymorphisms in Roma samples that implies clinical significance in this ethnic group.
BACKGROUND:Cytochrome P450 2B6 and 2D6 are important enzymes in human drug metabolism. These phase I enzymes are known to contribute the biotransformation of clinically important pharmaceuticals, including antidepressants, anticancer and anxiolytic drugs. The aim of this work was to determine the pharmacogenetic profile of CYP2B6 and CYP2D6 in Roma and Hungarian population samples. METHODS: A study population of 426 healthy Roma and 431 healthy Hungarian subjects were characterized for CYP2B6 c.516G>T, CYP2D6 c.100C>T and c.1846G>A polymorphisms using predesigned TaqMan Drug Metabolism Genotyping Real Time-PCR assays. RESULTS: We found significant differences in the presence of CYP2B6 c.516G>T (p<0.001), CYP2D6 c.100C>T (p=0.003) and c.1846G>A (p=0.022) between Hungarian and Roma population. The 516T allele frequency was 33.6% in the Roma group, 21.4% in Hungarians, whereas the minor CYP2D6 100T allele was present in 26.6% in Romas and 20.5% in Hungarians. The 1864A allele frequency was 22.5% in Roma and 18.1% in Hungarian samples. A significant increase was found in genotype frequencies for homozygous minor allele carrier Roma participants compared to Hungarians for CYP2B6 516TT and CYP2D6 100TT. The following CYP2D6 genotypes were identified in Roma samples: *1/*1 (55.4%), *1/*4 (2.1%), *1/*10 (3.1%), *4/*10 (38.7%), *10/*10 (0.7%). CONCLUSION: Our results demonstrate an increased minor allele frequency for CYP2B6 and CYP2D6 polymorphisms in Roma samples that implies clinical significance in this ethnic group.
Authors: Ha Hai Nguyen; Thuong Thi Huyen Ma; Nhung Phuong Vu; Quynh Thi Nhu Bach; Thang Hong Vu; Ton Dang Nguyen; Hai Van Nong Journal: Medicine (Baltimore) Date: 2019-05 Impact factor: 1.817