PGENI is initially targeting countries that have moderate to good health system infrastructure, but have insufficient resources to integrate individual patient genotyping into routine practice. The selection is based on a combination of the World Health Organisation (WHO) ranking of gross healthcare expenditure (per capita) for individual countries, and population sizes greater than 200,000 people. Overall there are 104 countries on the initial PGENI list representing 78% of the total world population. Five hundred DNA samples (250 male; 250 female) from healthy donors of each ethnic group (representing at least 10% of the population) from each country are being requested to screen for the frequency of functional polymorphism in genes involved in drug metabolism and transport, and drug target genes.
The WHO publishes an Essentials Medicine List representing the minimum drugs that should be available in all countries for regardless of health care expenditure. All systemic (oral/intravenous) drugs from the 13th and 14th WHO Essentials Medicines Lists were selected as target drugs for the PGENI project. Pubmed and the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB) were mined for genes involved in drug metabolism, transport and the target genes for each of the PGENI drugs. A total of 154 genes associated with 206 drugs were identified. Where there are known functional polymorphisms in any of the 154 PGENI genes, literature reported allele frequencies in different populations have been compiled and are presented in the form of maps and tables.
Ultimately all common ethnic groups in the 104 PGENI countries will be genotyped for known functional polymorphisms in PGENI genes. This will allow global genotype profiles to be constructed and provide a publicly available resource for polymorphism information and allele frequencies. From this information National Formulary Recommendations will be built and provided to the Ministry of Health departments in every PGENI country. These recommendations will be in the form of prioritization – highlighting clinically relevant polymorphisms of high frequency for each country that should be targeted for pharmacogenetics assessment in individuals where possible, and surveillance – suggesting closer monitoring for reduced drug response and/or increased toxicity based on high population allele frequencies where pharmacogenetics testing of individuals is not possible.