title: ABCG2 gene polymorphisms as risk factors for atorvastatin adverse reactions: a case-control study.
abstract: OBJECTIVE
  To explore the association between dose-related adverse drug reactions (ADRs) of atorvastatin and polymorphisms of ABCG2, taking into account the influence of CYP3A4 and SLCO1B1 genes.
  
  
  METHODS
  Sixty patients who experienced atorvastatin dose-related ADRs and 90 matched patients without ADRs were enrolled in the study. Genotyping for ABCG2 421C > A, CYP3A4*22, SLCO1B1 388A > G, SLCO1B1 521T > C variants was performed by real-time PCR.
  
  
  RESULTS
  Patients with ABCG2 421CA or AA genotypes had 2.9 times greater odds of developing atorvastatin dose-dependent ADRs (OR: 2.91; 95% CI: 1.22-6.95; p = 0.016) than those with ABCG2 421CC genotype. After adjustments for clinical and genetic risk factors, ABCG2 remained a statistically significant predictor of adverse drug reactions (OR: 2.75; 95% CI: 1.1-6.87; p = 0.03;). Also, carriers of SLCO1B1 521 TC or CC genotypes had 2.3 greater odds (OR: 1.03-4.98; 95% CI: 1.03-4.98; p = 0.043) of experiencing ADRs caused by atorvastatin in comparison with carriers of SLCO1B1 521 TT genotype.
  
  
  CONCLUSIONS
  Our study demonstrated an association between atorvastatin-induced ADRs and genetic variants in the ABCG2 gene.
authors.affiliation: Agency for Medicinal Products & Medical Devices, Zagreb, Croatia.
authors.forename: Nikica
authors.initials: N
authors.lastname: Mirošević Skvrce
authors.affiliation: Agency for Medicinal Products & Medical Devices, Zagreb, Croatia.
authors.forename: Viola
authors.initials: V
authors.lastname: Macolić Šarinić
authors.affiliation: Department of Internal Medicine, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Iveta
authors.initials: I
authors.lastname: Šimić
authors.affiliation: Department of Laboratory Diagnostics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Lana
authors.initials: L
authors.lastname: Ganoci
authors.affiliation: Department of Internal Medicine, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Diana
authors.initials: D
authors.lastname: Muačević Katanec
authors.affiliation: Department of Laboratory Diagnostics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Nada
authors.initials: N
authors.lastname: Božina
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D044466:Asian People; D000069059:Atorvastatin / Q000009:adverse effects*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D027361:Organic Anion Transporters / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027381:Liver-Specific Organic Anion Transporter 1; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D000069059:Atorvastatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: ABCG2; CYP3A4; SLCO1B1; adverse drug reactions; atorvastatin; gene polymorphism