Pharmacogenetics of drug-metabolizing enzymes in US Hispanics

Abstract

Although the Hispanic population is continuously growing in the United States, they are underrepresented in pharmacogenetic studies. This review addresses the need for compiling available pharmacogenetic data in US Hispanics, discussing the prevalence of clinically relevant polymorphisms in pharmacogenes encoding for drug-metabolizing enzymes. CYP3A5*3 (0.245-0.867) showed the largest frequency in a US Hispanic population. A higher prevalence of CYP2C9*3, CYP2C19*4, and UGT2B7 IVS1+985 A>G was observed in US Hispanic vs. non-Hispanic populations. We found interethnic and intraethnic variability in frequencies of genetic polymorphisms for metabolizing enzymes, which highlights the need to define the ancestries of participants in pharmacogenetic studies. New approaches should be integrated in experimental designs to gain knowledge about the clinical relevance of the unique combination of genetic variants occurring in this admixed population. Ethnic subgroups in the US Hispanic population may harbor variants that might be part of multiple causative loci or in linkage-disequilibrium with functional variants. Pharmacogenetic studies in Hispanics should not be limited to ascertain commonly studied polymorphisms that were originally identified in their parental populations. The success of the Personalized Medicine paradigm will depend on recognizing genetic diversity between and within US Hispanics and the uniqueness of their genetic backgrounds.

Conflict of interest statement

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Figures

Figure 1

Principal component analysis (PCA) results of the Hispanic individuals with Europeans, Africans and Native Americans. PC 1 vs. PC2 scatter plots based on autosomal markers (left plot). Ellipses are fitted to the PCA results on the autosomes (right plot). Reprinted from Bryc et al. [11] with permission.

Figure 2

Genome-wide allelic dissimilarity and genomic admixture of a Puerto Rican population (n=35), as compared to a reference population from Kentucky (n=40, including European- and African-Americans). Plot depicts allelic dissimilarities as a distance matrix for reference (top) and Puerto Ricans (bottom). Each square represents a pair of individuals. Data are shown with samples reordered according to nearest neighbor clustering (right panels) and random order (left panels). The darker the spot, the more genetically distant the individuals are.