Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health

AbstractBoth safety and efficacy of medical treatment can vary depending on the ethnogeographic background of the patient. One of the reasons underlying this variability is differences in pharmacogenetic polymorphisms in genes involved in drug disposition, as well as in drug targets. Knowledge and appreciation of these differences is thus essential to optimize population-stratified care. Here, we provide an extensive updated analysis of population pharmacogenomics in ten pharmacokinetic genes (CYP2D6,CYP2C19,DPYD,TPMT,NUDT15 andSLC22A1), drug targets (CFTR) and genes involved in drug hypersensitivity (HLA-A,HLA-B) or drug-induced acute hemolytic anemia (G6PD). Combined, polymorphisms in the analyzed genes affect the pharmacology, efficacy or safety of 141 different drugs and therapeutic regimens. The data reveal pronounced differences in the genetic landscape, complexity and variant frequencies between ethnogeographic groups. Reduced function alleles ofCYP2D6,SLC22A1 andCFTR were most prevalent in individuals of European descent, whereasDPYD andTPMT deficiencies were most common in  Sub-Saharan Africa. Oceanian populations showed the highest frequencies ofCYP2C19 loss-of-function alleles while their inferred CYP2D6 activity was among the highest worldwide. Frequencies ofHLA-B*15:02 andHLA-B*58:01 were highest across Asia, which has important implications for the risk of severe cutaneous adverse reactions upon treatment with carbamazepine and allopurinol.G6PD deficiencies wer...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research