Adrián LLerena
RIBEF Ibero-Latinoamerican Network of Pharmacogenetics, Spain
Title: CEIBA-MESTIFAR PROJECT: Population pharmacogenetics in Hispanic populations
Biography
Biography: Adrián LLerena
Abstract
The Iberian American Network of Pharmacogenetics and Pharmacogenomics (RIBEF) was created with the aim of promoting collaborative pharmacogenetic research in Iberoamerica. Latinoamericans are diverse according to their genetic composition resulting from the inter-ethnic crosses between Amerindians, Europeans and Africans. The genetic polymorphism of the most studied CYPs are among the major determinants of the interindividual and interethnic variability of pharmacokinetics and drug response. \\\"Poor metabolizers\\\" (PM), and \\\"extensive metabolizers\\\" (EM) including a group of Ultra-rapid Metabolizers (UMs) have been described for CYP2D6 and CYP2C19, and “slow metabolizers” (SMs) have been described for CYP2C9, Therefore the CEIBA-RIBEF Network Consortium (European Ibero-American for Population Pharmacogenetics) aimed to evaluate the most relevant CYPs genetic polymorphism (CYP2D6, CYP2C9, CYP2C19) in Hispanics from Ibero-America. An standardized protocol for genetic analyse has been developed. To date the CYP2D6-2C9-2C19 genetic polymorphism have been studied in 6013 healthy volunteers from North (n=756), Central (n=250) and South Mexico (n=545), Cuba (n=713), Nicaragua (n=133), Costa-Rica (n=458), Colombia (n=294), Ecuador (n=401), Brazil (n=98), Peru (n=286), Argentina (n=426), Chile (n=285), Uruguay (n=32), Portugal (n=458) and Spain (n=878). The frequency of CYP2D6 PMs and UMs in Spain is 7-10% and 4.9%, respectively (Llerena et al., 2009). Differences have been found across Hispanics: the frequency of CYP2D6 PMs ranged from 0% (some groups from Mexico and Peru) to 10% (Amerindians from Costa Rica) and for UMs from 0% (some groups from Mexico and Peru) to 20% (some Amerindian groups from Mexico). For CYP2C19, the frequency of PMs varied from 0 (some groups from Brazil, Costa Rica, Mexico and Nicaragua) to 3.46% (Admixed from Cuba), and for UMs from 0 (some groups from Costa Rica, Mexico and Peru) to 39.29% (Admixed from Brazil). The frequency of CYP2C9 SMs ranged from 0-0.85%. Present data shows a large variability on CYPs polymorphism across Hispanics. The pharmacogenetics of CYP2D6, CYP2C19 and CYP2C9 may be a useful tool to predict unexpected side-effects, interactions, or therapeutic failures of many relevant drugs and may explain the interethnic differences observed the response to several drugs. Financial Support: Government of Extremadura-AEXCID (13/A001) MESTIFAR to the RIBEF Network IberoAmerican Society of Pharmacogenetics SIFF (www.ribef.com).