Ganoci Lana, Božina Tamara, Mirošević Skvrce Nikica, Lovrić Mila, Mas Petar, Božina Nada
Drug Metab Pers Ther. 2017 Mar 1;32(1):11-21. doi: 10.1515/dmpt-2016-0024.
Data on the frequency of pharmacogenetic polymorphisms in the Croatian population are limited. We determined and analyzed frequencies for the most important CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 genetic variants in the Croatian population.
2637 subjects were included. Genotyping was performed by real-time polymerase chain reaction (PCR) using TaqMan® DME or TaqMan® SNP Genotyping Assays, and by PCR, and PCR-RFLP analysis.
For CYP2C9, allele frequencies of *2 and *3 variant were 14.5% and 7.6%, respectively. Among them, 3.98% of subjects were predicted to be poor metabolizers. For CYP2C19, the most frequent variant alleles were *2 (14.8%), and *17 (23.7%), while 2.4% of subjects were predicted to be poor metabolizers, and 5.39% were homozygous carriers of *17 predicted to be ultrarapid metabolizers (UM). For CYP2D6, the frequencies of tested variant alleles were *3 (2.2%), *4 (17.4%), *5 (1%), *6 (1.1%), and 41 (10.8%). Out of these, 5.59% were predicted to be poor metabolizers, 3.19% were classified as UM while 1.0% were carriers of variant alleles duplications (undefined phenotype). For CYP3A4 allele frequencies of 1B and 22 variants were 1.4% and 2.7%, respectively. Allele frequency of CYP3A53 was 95.5%. Analyzing CYP3A cluster according to the combination of CYP3A422 and CYP3A53 revealed 5.34% of subjects to be poor metabolizers, while 8.66% were classified as extensive metabolizers.
The frequency of the CYP allelic variants, genotypes, and predicted phenotypes in the Croatian population is in accordance with the other European populations, between the values of published data for Middle European and Mediterranean populations.
克罗地亚人群中药物遗传多态性频率的数据有限。我们测定并分析了克罗地亚人群中最重要的CYP2C9、CYP2C19、CYP2D6、CYP3A4和CYP3A5基因变体的频率。
纳入2637名受试者。使用TaqMan® DME或TaqMan® SNP基因分型检测试剂盒通过实时聚合酶链反应（PCR）、PCR以及PCR-RFLP分析进行基因分型。
对于CYP2C9，2和3变体的等位基因频率分别为14.5%和7.6%。其中，3.98%的受试者预计为慢代谢者。对于CYP2C19，最常见的变体等位基因为2（14.8%）和17（23.7%），而2.4%的受试者预计为慢代谢者，5.39%为17纯合携带者，预计为超快代谢者（UM）。对于CYP2D6，检测到的变体等位基因频率分别为3（2.2%）、4（17.4%）、5（1%）、6（1.1%）和41（10.8%）。其中，5.59%预计为慢代谢者，3.19%被归类为UM，而1.0%为变体等位基因重复携带者（未明确表型）。对于CYP3A4，1B和22变体的等位基因频率分别为1.4%和2.7%。CYP3A53的等位基因频率为95.5%。根据CYP3A422和CYP3A5*3的组合分析CYP3A簇，发现5.34%的受试者为慢代谢者，而8.66%被归类为广泛代谢者。
克罗地亚人群中CYP等位基因变体、基因型和预测表型的频率与其他欧洲人群一致，介于中欧和地中海人群已发表数据的值之间。
