title: Genetic variation in key genes associated with statin therapy in the Azores Islands (Portugal) healthy population.
abstract: BACKGROUND
  Inter-individual variation in response to statins (efficacy and toxicity) has been described and may be due to polymorphisms implicated in drug pharmacokinetics or pharmacodynamics.
  
  
  OBJECTIVE
  This study investigates clinically relevant pharmacogenes underlying statin response in 170 healthy Azoreans.
  
  
  METHODS
  Eight SNPs in candidate genes-HMGCR (rs3846662, rs17238540, rs17244841), CETP (rs708272), APOE (rs7412, rs429358) and SLCO1B1 (rs2306283, rs4149056)-were genotyped.
  
  
  RESULTS
  The allele frequencies were similar to those reported for European derived populations, excepting SLCO1B1 c.388A>G (rs2306283), which has a significant difference when compared with the HapMap CEU population (p = 1 × 10(-8)). The results of statin efficacy showed that 9.1% of Azoreans are APOE4 carriers. This allele has been associated with lower LDLc reduction from statin therapy and also higher LDLc levels at baseline. Regarding SLCO1B1, associated with statin toxicity, 1.8% of individuals have two reduced-function alleles (c.521CC).
  
  
  CONCLUSIONS
  The results contribute to overcome the lack of knowledge regarding the frequency of pharmacogenetic SNPs and their corresponding haplotypes in targeted populations, such as Azores islands. Moreover, the present work constitutes an initial step to implementing pharmacogenomics in clinical practice where physicians could use a patient's genetic make-up to optimize statin therapy, regarding efficiency and myopathy risk.
authors.affiliation: Molecular Genetics and Pathology Unit, Hospital of Divino Espírito Santo of Ponta Delgada , EPE, São Miguel Island, Azores , Portugal .
authors.forename: Mafalda S
authors.initials: MS
authors.lastname: Melo
authors.forename: Leticia
authors.initials: L
authors.lastname: Balanco
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Branco
authors.forename: Luisa
authors.initials: L
authors.lastname: Mota-Vieira
mesh_terms: D001394:Azores; D005260:Female; D005787:Gene Frequency; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Azores; cardiovascular diseases; pharmacogenetics; polymorphisms; statins