Influence of ethnicity on pharmacogenetic variation in the Ghanaian population.

It has been well established that the frequencies of genomic variants can vary greatly between the populations of different countries. We sought to quantify the intra-population variability in Ghana to determine the value of genotyping studies done at a nationwide level. Further, we investigated the differences between the Ghanaian and other African populations to determine the quality of genomic representation provided by a small subgroup within the continent with regard to the general population. We genotyped 934 unrelated Ghanaian individuals for 15 single nucleotide polymorphisms (SNPs) from genes defined as clinically relevant based on their reported roles in the transport of, metabolism of, or as targets of the medicines listed in the World Health Organization Essential Medicines list. Populations within Ghana and between nations in Western Africa were genetically cohesive. In contrast, populations in other areas of Africa were genetically divergent. Gene allele frequency also differed significantly between the populations in African nations and the United States for several of the SNPs. These results demonstrate that national populations in similar geographic regions, like Africa, may have widely varying genetic allele frequencies for clinically relevant SNPs. Further genotyping studies of specific populations are necessary to provide the best medical care to all individuals.

Ethnic differences in pharmacogenetically relevant genes.

There is great heterogeneity in the way humans respond to medications, often requiring empirical strategies to define the appropriate drug therapy for each patient. Genetic polymorphisms in drug metabolizing enzymes, transporters, receptors, and other drug targets provide putative markers for predicting which patients will experience extreme toxicity and treatment failure. Both quantitative (allele frequency) and qualitative (specific allele) differences for polymorphic genes have been observed between different population groups. For example, the frequency of mutations in thiopurine methyltransferase is lower in Chinese than Caucasian populations. In addition, the predominant mutation responsible for deficient enzyme activity differs between the two populations (TPMT*l3C versus TPMT*3A). Understanding the influence of ethnicity on pharmacogenomics will allow for comprehensive strategies for using the genome to optimize therapy for patients throughout the world.