Influence of PPARA, RXRA, NR1I2 and NR1I3 gene polymorphisms on the lipid-lowering efficacy and safety of statin therapy.
OBJECTIVE
The aim of the present study was investigate the association between six genetic variants in the nuclear receptor genes PPARA, RXRA, NR1I2 and NR1I3 and the lipid-lowering efficacy and safety of statin therapy.


METHODS
The study was carried out on 240 Brazilian hypercholesterolemic patients on simvastatin and atorvastatin therapy. The polymorphisms were analyzed by PCR-based methods.


RESULTS
The NR1I3 rs2307424 genotype distribution was different between subjects with and without adverse drug reactions. Among subjects in the ADR group, no T/T homozygotes were observed for this polymorphism, while in the non-ADR group the frequency of this genotype was 19.4% (P = 0.007, after multiple testing corrections P = 0.042).


CONCLUSIONS
The polymorphisms investigated in PPARA (rs1800206), RXRA (rs11381416), and NR1I2 (rs1523130) did not influence the lipid-lowering efficacy and safety of statin. Our results show the possible influence of NR1I3 genetic variant on the safety of statin.
Luciana Otero
LO
Lima
Estela Maria
EM
Bruxel
Mara Helena
MH
Hutz
Cézar Roberto
CR
Van der Sand
Luiz Carlos
LC
Van der Sand
Maria Elvira Wagner
ME
Ferreira
Renan Canibal
RC
Pires
Marilu
M
Fiegenbaum
Silvana
S
Almeida
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069059:Atorvastatin; D000090702:Constitutive Androstane Receptor; D050171:Dyslipidemias / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D000077297:Pregnane X Receptor; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics*; D047490:Retinoid X Receptor alpha / Q000235:genetics*; D012307:Risk Factors; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D000090702:Constitutive Androstane Receptor; D006538:Heptanoic Acids; D008055:Lipids; C000625852:NR1I2 protein, human; C000716327:NR1I3 protein, human; D047493:PPAR alpha; D000077297:Pregnane X Receptor; D011758:Pyrroles; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D047490:Retinoid X Receptor alpha; D000069059:Atorvastatin; D019821:Simvastatin