title: CYP2C9 and VKORC1 genotypes in Puerto Ricans: A case for admixture-matching in clinical pharmacogenetic studies.
abstract: BACKGROUND
  Admixture is of great relevance to the clinical application of pharmacogenetics and personalized medicine, but unfortunately these studies have been scarce in Puerto Ricans. Besides, allele frequencies for clinically relevant genetic markers in warfarin response (i.e., CYP2C9 and VKORC1) have not yet been fully characterized in this population. Accordingly, this study is aimed at investigating whether a correlation between overall genetic similarity and CYP2C9 and/or VKORC1 genotypes could be established.
  
  
  METHODS
  98 DNA samples from Puerto Ricans were genotyped for major CYP2C9 and VKORC1 polymorphisms and tested on a physiogenomic (PG)-array to infer population structure and admixture pattern.
  
  
  RESULTS
  Analysis affirmed that Puerto Ricans are broadly admixed. A genetic distance dendrogram was constructed by clustering those subjects with similar genetic profiles. Individual VKORC1 and CYP2C9 genotypes were visually overlaid atop the three dendrogram sectors. Sector-1, representing Amerindian ancestry, showed higher VKORC1 -1639G>A variant frequency than the rest of the population (p=0.051). Although CYP2C9*3 allele frequencies matched the expected HapMap values, admixture may explain deviations from published findings regarding VKORC1 -1639G>A and CYP2C9*2 allele frequencies in sector-3.
  
  
  CONCLUSIONS
  Results suggest that the observed inter-individual variations in ancestral contributions have significant implications for the way each Puerto Rican responds to warfarin therapy. Our findings provide valuable evidence on the importance of controlling for admixture in pharmacogenetic studies of Puerto Rican Hispanics.
authors.affiliation: Laboratory of Personalized Health, Genomas, Inc., Hartford, CT 06106, USA.
authors.forename: David
authors.initials: D
authors.lastname: Villagra
authors.forename: Jorge
authors.initials: J
authors.lastname: Duconge
authors.forename: Andreas
authors.initials: A
authors.lastname: Windemuth
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Cadilla
authors.forename: Mohan
authors.initials: M
authors.lastname: Kocherla
authors.forename: Krystyna
authors.initials: K
authors.lastname: Gorowski
authors.forename: Kali
authors.initials: K
authors.lastname: Bogaard
authors.forename: Jessica Y
authors.initials: JY
authors.lastname: Renta
authors.forename: Irelys A
authors.initials: IA
authors.lastname: Cruz
authors.forename: Sara
authors.initials: S
authors.lastname: Mirabal
authors.forename: Richard L
authors.initials: RL
authors.lastname: Seip
authors.forename: Gualberto
authors.initials: G
authors.lastname: Ruaño
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics; D011647:Puerto Rico; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases