de la Cruz Carla González, Guevara Mariela, Rodrigues-Soares Fernanda, Rodríguez Ernesto, Peñas-Lledó Eva, LLerena Adrián, Dorado Pedro
Personalized Medicine and Mental Health Unit, INUBE University Institute for Bio-Sanitary Research of Extremadura, 06080 Badajoz, Spain.
Pharmacogenetic and Pharmacogenomics Unit, Extremadura Health Service, Badajoz University Hospital, Extremadura University, 06080 Badajoz, Spain.
Genes (Basel). 2025 Apr 30;16(5):540. doi: 10.3390/genes16050540.
A variable number tandem repeat polymorphism has been described in the promoter (pVNTR) with three types of fragments: short (), medium (), and long (). The allele appears in strong linkage disequilibrium (LD) with the non-functional allele in populations of European ancestry, but independently of this, it also appears to reduce the level of CYP2C9 expression in human liver by up to 34%.
This study, in a Dominican population with varying amounts of Western European, African, and Native American ancestry, aims primarily to determine the frequency of pVNTR, and the degree of LD of with Secondarily, it explores if the frequency of the allele is over- or under-represented in those with a greater component of African ancestry.
A total of 193 healthy volunteers from the Dominican Republic participated in the study. The promoter region of was amplified and analyzed by capillary electrophoresis. Analyses of genotypes (, , , , and ) and genetic ancestry, estimated in 176 Dominican individuals by genotyping 90 ancestry informative markers, were previously performed in this population.
The frequencies of , and variants are 0.065, 0.896, and 0.039, respectively. LD between and was found (D' = 0.756, r = 0.702) to be weaker than in European populations.
Populations with a greater African ancestry component appear to present a lower-than-expected frequency of , as well as a lower tendency for this and alleles to be inherited together, as is common in Europeans. The present exploratory results warrant further research in vivo about the effects of in predicting activity. Its inclusion in testing panels for personalized drug therapy could be relevant in populations such as the Dominican, where the LD between and is low.
已在启动子中描述了一种可变数目串联重复多态性（pVNTR），其具有三种类型的片段：短片段（）、中片段（）和长片段（）。在欧洲血统人群中， 等位基因与无功能的 等位基因呈现出强连锁不平衡（LD），但除此之外，它似乎还能使人类肝脏中CYP2C9的表达水平降低多达34%。
本研究针对具有不同比例西欧、非洲和美洲原住民血统的多米尼加人群，主要目的是确定pVNTR的频率，以及 与 的连锁不平衡程度。其次，探讨在非洲血统占比更大的人群中， 等位基因的频率是否过高或过低。
共有193名来自多米尼加共和国的健康志愿者参与了该研究。通过毛细管电泳对CYP2C9的启动子区域进行扩增和分析。此前已对该人群中176名多米尼加个体的CYP2C9基因型（， ， ， ，和 ）以及通过对90个祖先信息标记进行基因分型估计的遗传血统进行了分析。
、 和 变体的频率分别为0.065、0.896和0.039。发现 与 之间的连锁不平衡（D' = 0.756，r = 0.702）比欧洲人群中的要弱。
非洲血统占比更大的人群中， 的频率似乎低于预期，并且该等位基因与 等位基因一起遗传的倾向也较低，而在欧洲人群中这种情况很常见。目前的探索性结果值得进一步开展关于 在预测CYP2C9活性方面作用的体内研究。在多米尼加这样的人群中，将其纳入个性化药物治疗的CYP2C9检测面板可能具有重要意义，因为在这些人群中 与 之间的连锁不平衡较低。
