Guevara Mariela, Rodrigues-Soares Fernanda, de la Cruz Carla González, de Andrés Fernando, Rodríguez Ernesto, Peñas-Lledó Eva, LLerena Adrián
Facultad de Ciencias de la Salud, Universidad Nacional Pedro Henríquez Ureña, Santo Domingo 10514, Dominican Republic.
Faculty of Medicine and Health Sciences, University Institute for Bio-Sanitary Research of Extremadura INUBE, University of Extremadura, 06006 Badajoz, Spain.
Pharmaceutics. 2024 Oct 30;16(11):1399. doi: 10.3390/pharmaceutics16111399.
: Research on pharmacogenetic variability in response to prescribed drugs and across ethnic groups is essential for personalized medicine, particularly in admixed and unstudied populations. For the first time, this study examines , , and alleles and genotypes in 197 healthy volunteers from the Dominican Republic, as part of the RIBEF-CEIBA collaborative network. : The analysis focuses on the participants' tri-hybrid genomic ancestry, with CYP alleles determined by real-time PCR and molecular ancestry inferred using 90 AIMs. Linear regression was used to associate ancestry components with CYP frequencies. : The average ancestry was 23.8% European, 42.6% Native American, and 33.6% African, the latter being higher than in most Latin American populations. Native American ancestry was also higher than expected. Predicted phenotype frequencies based on genotypes were 4.2% poor metabolizers (gPMs) and 3.6% ultrarapid metabolizers (gUMs) for CYP2D6, as well as 3% gPMs, 22.8% rapid metabolizers (gRMs), and 1.5% gUMs for CYP2C19. No gPM individuals were observed for CYP2C9. Certain alleles associated with decreased CYP2D6 activity ( and ) and increased CYP2C19 activity ( and gUMs) were positively linked with African ancestry and negatively with Native American ancestry. Rare alleles ( and ) with clinical relevance were additionally found. : These findings build on previous results from the RIBEF-CEIBA collaborative network, demonstrating differences in allele frequencies of , , and in relation to genomic ancestry. In summary, ethnicity must be considered in the development of pharmacogenetic guidelines for clinical application, research, and regulation to avoid widening the biotechnology gap and to allow Personalized Medicine to reach the entire world population.
针对处方药反应及不同种族间的药物遗传变异性研究对于个性化医疗至关重要，尤其是在混合人群和未充分研究的人群中。本研究首次作为RIBEF - CEIBA合作网络的一部分，对来自多米尼加共和国的197名健康志愿者的[具体基因名称]、[具体基因名称]和[具体基因名称]等位基因及基因型进行了检测。分析聚焦于参与者的三杂种基因组血统，通过实时PCR确定CYP等位基因，并使用90个祖先信息标记（AIMs）推断分子血统。采用线性回归将血统成分与CYP频率相关联。平均血统为23.8%欧洲血统、42.6%美洲原住民血统和33.6%非洲血统，非洲血统比例高于大多数拉丁美洲人群。美洲原住民血统也高于预期。基于基因型预测的表型频率，CYP2D6的慢代谢者（gPMs）为4.2%，超快代谢者（gUMs）为3.6%；CYP2C19的gPMs为3%，快代谢者（gRMs）为22.8%，gUMs为1.5%。未观察到CYP2C9的gPM个体。某些与CYP2D6活性降低相关的等位基因（[具体等位基因名称]和[具体等位基因名称]）以及与CYP2C19活性增加相关的等位基因（[具体等位基因名称]和gUMs）与非洲血统呈正相关，与美洲原住民血统呈负相关。还发现了具有临床相关性的罕见[具体等位基因名称]等位基因（[具体等位基因名称]和[具体等位基因名称]）。这些发现基于RIBEF - CEIBA合作网络先前的结果，证明了[具体基因名称]、[具体基因名称]和[具体基因名称]等位基因频率与基因组血统的差异。总之，在制定临床应用、研究和监管的药物遗传学指南时必须考虑种族因素，以避免扩大生物技术差距，并使个性化医疗惠及全球所有人。
