Pharmacogenetics of healthy volunteers in Puerto Rico

Abstract

Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer’s disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island.

Assessment of the clinical utility of pharmacogenetic guidance in a comprehensive medication management service

“…While PGx variability among patients worldwide is well‐documented, studies in Hispanics are scarce. Puerto Ricans are genetically distinct from other Hispanics due to the admixture from several parental groups 9,10 . Accordingly, it is a diverse population that could certainly benefit from PGx guidance.…”

Results and challenges of Cytochrome P450 2D6 (CYP2D6) testing in an ethnically diverse South Florida population

“…Notably, *10 has conflicting data on several Puerto Rican populations. One study stated that *10 was found less frequently than in Caucasian populations, while another reported that Puerto Ricans have a *10 frequency similar to Caucasians (Claudio‐Campos, Orengo‐Mercado, et al, ).…”

“…Thus, pharmacogenetic test results would be more useful and accurate if laboratories sequenced the entire CYP2D6 gene, rather than selected polymorphisms. As a whole, sequencing would also provide a better depiction of the allelic variation within underrepresented communities (Barron et al, ; Bernard, ; Claudio‐Campos, Orengo‐Mercado, et al, ; Ortega & Meyers, ). Importantly, minority groups are predicted to become the majority by 2044, with a quarter being Hispanic (Colby & Ortman, ).…”

The Puerto Rico Alzheimer Disease Initiative (PRADI): A Multisource Ascertainment Approach

“…Second, the PRADI study makes comparisons using two types of controls: family-based (related controls) and case-control (unrelated controls), paralleling, and building on the ongoing work of the ADSP (Beecham et al, 2017). Furthermore, Puerto Ricans are an admixed population, enriched for at least three ancestries (European Caucasian, Western African, and Amerindian/Taino), resulting in complex population substructure (Claudio-Campos et al, 2015; Rajabli et al, 2018). The use of population substructure (i.e., global and local ancestry) can allow for adjustment of models to improve genetic analyses.…”