title: PON1 polymorphisms are predictors of ability to attain HDL-C goals in statin-treated patients.
abstract: OBJECTIVE
  PON1 plays an important role in inhibiting LDL-C oxidation, which reduces atherosclerosis and cardiovascular disease. Elevated PON1 activity or levels may contribute to increased HDL-C levels, but controversy exists over the hypothesis that genetic variation in the PON1 gene locus modulates HDL-C levels and responses to statin treatment. Therefore, the objective of this study was to investigate the association between two polymorphisms in the PON1 gene and statin responses in a south Brazilian population.
  
  
  METHODS
  The study population included 433 dyslipidemic patients who were prescribed statins. Total cholesterol, triglyceride, HDL-C and LDL-C levels were measured in these patients both before and after approximately 6months of treatment with simvastatin/atorvastatin. Genotypes were assessed by real-time PCR for two PON1 polymorphisms, Q192R (rs662) and L55M (rs854560).
  
  
  RESULTS
  Baseline lipid levels were not associated with Q192R or L55M polymorphisms. For the Q192R (rs662) polymorphism, we observed that HDL-C goals were attained less often in patients with RR homozygosity than in Q allele carriers (χ(2) P=0.009, adjusted residual analysis P=0.003). For the L55M (rs854560) polymorphism, LL homozygotes were underrepresented among subjects that achieved the HDL-C goal (χ(2) P=0.026, adjusted residual analysis P=0.008). Analysis by univariate logistic regression confirmed that QQ/QR and MM/ML carriers had an increased chance of attaining HDL-C goals (OR=2.41, CI95%=1.32-4.40, P=0.004 and OR=1.68, CI95%=1.15-2.45, P=0.008). In a multivariate logistic analysis used to assess predictors of attaining an HDL-C goal>1.55mmol/L, we observed that gender (OR=1.71, CI95%=1.04-2.83, P=0.036), baseline HDL-C levels (OR=1.13, CI95%=1.10-1.16, P<0.001) and the QQ/QR+MM/ML genotypes increased the chance of achieving HDL-C goals (OR=2.81, CI95%=1.35-5.85, P=0.006).
  
  
  CONCLUSIONS
  The results of this study show that the Q192R (rs662) and L55M (rs854560) polymorphisms may play a role in interindividual variation in achievement of HDL-C goals in response to statins.
authors.affiliation: Programa de Pós-Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre-UFCSPA, Rio Grande do Sul, Brazil.
authors.forename: Jéssica Aguiar
authors.initials: JA
authors.lastname: de Souza
authors.affiliation: Programa de Pós-Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre-UFCSPA, Rio Grande do Sul, Brazil.
authors.forename: Angelica
authors.initials: A
authors.lastname: Menin
authors.affiliation: Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul-UFRGS, Rio Grande do Sul, Brazil.
authors.forename: Luciana Otero
authors.initials: LO
authors.lastname: Lima
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre-UFCSPA, Rio Grande do Sul, Brazil.
authors.forename: Lisiane
authors.initials: L
authors.lastname: Smiderle
authors.affiliation: Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul-UFRGS, Rio Grande do Sul, Brazil.
authors.forename: Mara Helena
authors.initials: MH
authors.lastname: Hutz
authors.affiliation: Centro de Diagnóstico Cardiológico, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Cézar Roberto
authors.initials: CR
authors.lastname: Van Der Sand
authors.affiliation: Centro de Diagnóstico Cardiológico, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Van Der Sand
authors.affiliation: Centro de Diagnóstico Cardiológico, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Maria Elvira Wagner
authors.initials: ME
authors.lastname: Ferreira
authors.affiliation: Centro de Diagnóstico Cardiológico, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Renan Canibal
authors.initials: RC
authors.lastname: Pires
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre-UFCSPA, Rio Grande do Sul, Brazil.
authors.forename: Silvana
authors.initials: S
authors.lastname: Almeida
authors.affiliation: Programa de Pós-Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre-UFCSPA, Rio Grande do Sul, Brazil; Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre-UFCSPA, Rio Grande do Sul, Brazil. Electronic address: mariluf@ufcspa.edu.br.
authors.forename: Marilu
authors.initials: M
authors.lastname: Fiegenbaum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics*; D000069059:Atorvastatin / Q000627:therapeutic use; D001938:Brazil; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000069059:Atorvastatin; D019821:Simvastatin; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Dyslipidemia; HDL-C; LDL-C; PON1; Paraoxonase; Statins