Genetics
CETP TaqI and -629C/A variants predict a bigger HDL-C rise on atorvastatin, while CETP 405I/V predicts higher MI risk in CAD patients (DNA Cell Biol 2010)
Original title: Common variants of HMGCR, CETP, APOAI, ABCB1, CYP3A4, and CYP7A1 genes as predictors of lipid-lowering response to atorvastatin therapy
Studying 18 SNPs across six lipid- and statin-metabolism genes (HMGCR, CETP, APOAI, ABCB1, CYP3A4, CYP7A1) in 265 newly diagnosed coronary artery disease patients treated with atorvastatin 20 mg/day, researchers found variant alleles of CETP TaqI and -629C/A, along with APOAI PstI, associated with a greater HDL-C increase, while several HMGCR, ABCB1, and CYP7A1 variants were associated with attenuated LDL-C reduction. A three-locus interaction model (CYP7A1 rs892871 AA, APOAI PstI P1P1, HMGCR rs12916 CT) predicted LDL-C lowering better than single-polymorphism analysis. Over one year of follow-up, variant genotypes of APOAI -2500C/T, CETP 405I/V, and ABCB1 3435C/T were associated with higher risk of myocardial infarction (P less than 0.05), linking specific CETP variants to both statin-response and cardiovascular-event risk in this cohort.
Original abstract
There is interindividual variation in lipid-lowering response to statins. The objective of this study was to investigate whether common variation in genes involved in lipid and statin metabolism modify the effect of statins on serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol concentration in coronary artery disease (CAD) patients. We studied the association between 18 single-nucleotide polymorphisms (SNPs) in six genes (HMGCR, CETP, APOAI, ABCB1, CYP3A4, CYP7A1) in response to atorvastatin therapy (20 mg/day) in 265 newly diagnosed CAD patients using multivariable adjusted general linear regression. Variant alleles of ABCB1 (-41A/G), HMGCR SNP29 G/T, rs5908A/G, rs12916C/T, and CYP7A1-204A/C polymorphisms were significantly associated with attenuated LDL-C reduction and variant alleles of CETP TaqI, -629C/A, and APOAI PstI polymorphisms were associated with higher increase in high-density lipoprotein-cholesterol. A three-loci interaction model consisting of CYP7A1rs892871AA/APOAIPstIP1P1/HMGCR rs12916CT was a better predictor for LDL-C lowering, when compared with single polymorphisms analysis on statin response. Variant genotypes of APOAI -2500C/T, CETP 405I/V, and ABCB1 3435C/T showed higher risk of myocardial infarction events (p < 0.05) in a 1-year follow-up of CAD patients. These results suggest that SNPs in lipid and statin pathway genes are associated with reduced LDL-C lowering by statins and identify individuals who may be resistant to maximal LDL-C lowering by statins.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.