BACKGROUND: In recent years, one of the focuses of genetic investigation in cardiology has been to identify the genetic factors associated with variable response to statin treatment. Polymorphisms in apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC), proteins with major roles in lipid metabolism and homeostasis have been shown associated with lipid-lowering drugs response. METHODS: One hundred forty-six hypercholesterolemic patients of European descent were prospectively enrolled and treated with simvastatin 20 mg per day for over 6 months. Ninety-nine subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. APOE (E*2, E*3 and E*4), LIPC-250A > G and CETP TaqIB genotypes were determined by PCR and restriction mapping. RESULTS: After a 6-month follow-up, no differences among genotypes in the percentage variation in lipid and lipoprotein concentrations for APOE and LIPC SNPs were observed. After adjustment for covariates, CETP B2B2 homozygotes showed a greater HDL-cholesterol increase compared to B1B2 and B1B1 subjects (14.1% vs. 1.7% and 1.3%, P < 0.05, respectively). CONCLUSION: Our study demonstrates that individual plasma HDL-cholesterol response to simvastatin is mediated, in part, by the CETP gene locus, with the B2 homozygotes having more benefit in HDL-C improvement than carriers of B1 allele.
BACKGROUND: In recent years, one of the focuses of genetic investigation in cardiology has been to identify the genetic factors associated with variable response to statin treatment. Polymorphisms in apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC), proteins with major roles in lipid metabolism and homeostasis have been shown associated with lipid-lowering drugs response. METHODS: One hundred forty-six hypercholesterolemicpatients of European descent were prospectively enrolled and treated with simvastatin 20 mg per day for over 6 months. Ninety-nine subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. APOE (E*2, E*3 and E*4), LIPC-250A > G and CETP TaqIB genotypes were determined by PCR and restriction mapping. RESULTS: After a 6-month follow-up, no differences among genotypes in the percentage variation in lipid and lipoprotein concentrations for APOE and LIPC SNPs were observed. After adjustment for covariates, CETP B2B2 homozygotes showed a greater HDL-cholesterol increase compared to B1B2 and B1B1 subjects (14.1% vs. 1.7% and 1.3%, P < 0.05, respectively). CONCLUSION: Our study demonstrates that individual plasma HDL-cholesterol response to simvastatin is mediated, in part, by the CETP gene locus, with the B2 homozygotes having more benefit in HDL-C improvement than carriers of B1 allele.
Authors: Lucia A Hindorff; Rozenn N Lemaitre; Nicholas L Smith; Joshua C Bis; Kristin D Marciante; Kenneth M Rice; Thomas Lumley; Daniel A Enquobahrie; Guo Li; Susan R Heckbert; Bruce M Psaty Journal: Pharmacogenet Genomics Date: 2008-08 Impact factor: 2.089
Authors: L Smiderle; M Fiegenbaum; M H Hutz; C R Van Der Sand; L C Van Der Sand; M E W Ferreira; R C Pires; S Almeida Journal: Pharmacogenomics J Date: 2015-08-25 Impact factor: 3.550
Authors: Alvaro Cerda; Fabiana D V Genvigir; Maria A V Willrich; Simone S Arazi; Marcia M S Bernik; Egidio L Dorea; Marcelo C Bertolami; Andre A Faludi; Mario H Hirata; Rosario D C Hirata Journal: Lipids Health Dis Date: 2011-11-10 Impact factor: 3.876
Authors: Lisiane Smiderle; Luciana O Lima; Mara Helena Hutz; Cézar Roberto Van der Sand; Luiz Carlos Van der Sand; Maria Elvira Wagner Ferreira; Renan Canibal Pires; Silvana Almeida; Marilu Fiegenbaum Journal: Arq Bras Cardiol Date: 2014-07 Impact factor: 2.000