title: Pharmacogenetic profile of a South Portuguese population: results from the pilot study of the European Health Examination Survey in Portugal.
abstract: BACKGROUND
  The genetic inter-individual variability of drug response can lead to therapeutic failure or adverse drug reactions (ADRs). The aims of this study were to assess the pharmacogenetic profile of a South Portuguese population according to established dosing guidelines for commonly prescribed drugs and to compare it with that of previously genotyped populations.
  
  
  METHODS
  A cross-sectional study was developed in the context of the Portuguese Component of the European Health Examination Survey (EHES). A total of 47 pharmacogenetically relevant variants in 23 different genes were genotyped in 208 participants. Allelic and genotypic frequencies were calculated, and the pharmacogenetic profile of the participants was defined. A comparative analysis was conducted through electronic database search. Pairwise Fst calculations were performed to assess the genetic distance between populations.
  
  
  RESULTS
  We found a significant small differentiation between the Portuguese regional populations regarding CYP2C9 rs1057910, CYP2D6 rs3892097, MTHFR rs1801133 and F5 rs6025. When consid-ering 4 HapMap populations, ADH1B rs2066702, ADH1B rs1229984, NAT2 rs1799931 and VKORC1 rs9923231 displayed a significant population differentiation. We found that 18.9% of the participants are intermediate or poor metabolizers for at least 3 drugs simultaneously and that 84.6% of the participants have at least one therapeutic failure or ADR risk allele for the considered drugs.
  
  
  CONCLUSIONS
  There is a high prevalence of risk alleles associated with an altered drug metabolism regarding drugs largely used by the South Portuguese population. This knowledge contributes to the prediction of their clinical efficacy and/or toxicity, optimizing therapeutic response while improving cost-effectiveness.
authors.affiliation: Departamento de Epidemiologia, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal.
authors.forename: Vânia
authors.initials: V
authors.lastname: Gaio
authors.forename: Isabel
authors.initials: I
authors.lastname: Picanço
authors.forename: Baltazar
authors.initials: B
authors.lastname: Nunes
authors.forename: Aida
authors.initials: A
authors.lastname: Fernandes
authors.forename: Francisco
authors.initials: F
authors.lastname: Mendonça
authors.forename: Filomena
authors.initials: F
authors.lastname: Horta Correia
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Beleza
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Gil
authors.forename: Mafalda
authors.initials: M
authors.lastname: Bourbon
authors.forename: Astrid
authors.initials: A
authors.lastname: Vicente
authors.forename: Carlos
authors.initials: C
authors.lastname: Matias Dias
authors.forename: Marta
authors.initials: M
authors.lastname: Barreto da Silva
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation / Q000187:drug effects*; D005828:Genetics, Population / Q000379:methods; D055106:Genome-Wide Association Study; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods / Q000706:statistics & numerical data; D010865:Pilot Projects; D011174:Portugal; D055553:Prescription Drugs / Q000494:pharmacology; D044465:White People
chemical_list: D055553:Prescription Drugs