title: Genetic variants in genes related to lipid metabolism and atherosclerosis, dyslipidemia and atorvastatin response.
abstract: OBJECTIVE
  Using candidate gene approach, we have investigated the effect of single nucleotide polymorphism (SNP) in genes related to lipid metabolism and atherosclerosis on dyslipidemia and atorvastatin response.
  
  
  METHODS
  The study included 157 patients treated with atorvastatin and 145 controls. Genomic DNA was isolated and genotyped using SNPlex technology.
  
  
  RESULTS
  Allele and genotype disease association test revealed that APOB rs693 (OR: 2.2 [1.5-3.2], p=0.0001) and CD36 rs1984112 (OR: 3.7 [1.9-7.0], p=0.0002) SNPs were independent risk factors for hypercholesterolemia. Only APOB rs693 T variant allele was associated with increased LDL cholesterol levels (>160mg/dL). After atorvastatin treatment (10mg/day/4weeks), LIPC -514T allele was positively associated with LDL cholesterol reduction.
  
  
  CONCLUSIONS
  The current study reinforces the current knowledge that carrying APOB rs693 is an independent risk factor for dyslipidemia and higher LDL levels. Furthermore, we found that a variant of CD36 was associated with dyslipidemia as a risk (rs1984112) factor. Finally, atorvastatin response could be predicted by LIPC -514C>T SNP and physical activity. In conclusion, our data evidences the contribution of genetic markers and their interaction with environmental factor in the variability of statin response.
authors.affiliation: Faculdade de Ciências Farmacêuticas, USP, São Paulo, SP, Brazil. alice-rodrigues@usp.br
authors.forename: A C
authors.initials: AC
authors.lastname: Rodrigues
authors.forename: B
authors.initials: B
authors.lastname: Sobrino
authors.forename: F D V
authors.initials: FD
authors.lastname: Genvigir
authors.forename: M A V
authors.initials: MA
authors.lastname: Willrich
authors.forename: S S
authors.initials: SS
authors.lastname: Arazi
authors.forename: E L
authors.initials: EL
authors.lastname: Dorea
authors.forename: M M S
authors.initials: MM
authors.lastname: Bernik
authors.forename: M
authors.initials: M
authors.lastname: Bertolami
authors.forename: A A
authors.initials: AA
authors.lastname: Faludi
authors.forename: M J
authors.initials: MJ
authors.lastname: Brion
authors.forename: A
authors.initials: A
authors.lastname: Carracedo
authors.forename: M H
authors.initials: MH
authors.lastname: Hirata
authors.forename: R D C
authors.initials: RD
authors.lastname: Hirata
mesh_terms: D050197:Atherosclerosis / Q000150:complications*; D000069059:Atorvastatin; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006538:Heptanoic Acids / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin