Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly

Akao, H. et al. (2012) Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly. Atherosclerosis, 220(2), pp. 413-417. (doi:10.1016/j.atherosclerosis.2011.09.028)

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Abstract

Our goal was to determine whether genetic variation at genes affecting statin metabolism or targets of statin therapy would influence low density lipoprotein (LDL) cholesterol lowering with pravastatin, baseline heart disease, or cardiac endpoints on trial. We examined associations of single nucleotide polymorphisms (SNPs) at the liver X receptor alpha (LXRA, rs12221497), and the solute carrier organic anion transporter (SLCO1B1, rs4149056 and rs2306283) gene loci with these variables. We studied 5411 participants in PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) (mean age 75.3 years), who had been randomized to pravastatin 40 mg/day or placebo and were followed for a mean of 3.2 years. No relationships between genetic variation at the LXRA gene locus with statin induced LDL lowering response or other parameters were noted. Both the SLCO1B1 rs4149056 (valine for alanine at 174) and the rs2306283 (asparagine for aspartic acid at 130) SNPs affect the amino acid sequence of the SLCO1B1 gene product. No effect of the rs2306283 SNP on any of the variables was noted. However the presence of the rs4149056 SNP was associated with significantly less LDL cholesterol lowering response to pravastatin (wildtype, 71.5% of the population, −37.0%; heterozygotes, 25.8% of the population, −36.0%; and homozygotes, 2.7% of the population, −31.8%, p = 0.003 at 6 months, and p = 0.022 at 12 months). Our data indicate that the presence of the rs4149056 non-synonymous SNP at the SLCO1B1 gene locus can significantly decrease the pravastatin induced LDL cholesterol lowering response.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robertson, Mrs Michele and Ford, Professor Ian and Shepherd, Prof James and Packard, Professor Chris
Authors: Akao, H., Polisecki, E., Kajinami, K., Trompet, S., Robertson, M., Ford, I., Jukema, J.W., de Craen, A.J.M., Westendorp, R.G.J., Shepherd, J., Packard, C., Buckley, B.M., and Schaefer, E.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Atherosclerosis
Publisher:Elsevier Ireland Ltd
ISSN:0021-9150
ISSN (Online):1879-1484
Published Online:21 September 2011

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
382731Pharmacogenics of the statin response (PROSPER STUDY)James ShepherdNational Institutes of Health (NIH-NHLBI)01 HL074753SCHOOL OF MEDICINE