Related Experiment Video
Updated: Jul 14, 2026

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
Pharmacogenetic interaction between paraoxonase-1 gene promoter polymorphism C-107T and statin
Sara Deakin1, Sophie Guernier, Richard W James
1Clinical Diabetes Unit, Service of Endocrinology, Diabetes and Nutrition, University Hospital, Geneva, Switzerland.
Objective:
The aims of this study were to compare the impact of transcription factors, together with statin, on the paraoxonase promoter alleles defined by the C(-107T) polymorphism and to more clearly define regions of the paraoxonase promoter implicated in the actions of transcription factors.
Methods:
Expression studies of promoter alleles were performed with reporter gene cassettes transfected into HepG2 cells, complemented by nuclease protection assays, electrophoretic mobility shift assays and statin therapy in patients.
Results:
One region only of the minimal promoter fragment that up-regulates activity was protected by transcription factors and nuclear extracts. It spanned nucleotides -119 to -100, encompassing the C(-107)T polymorphism. Sp1 was effective alone in protecting this region, with its effect greatly enhanced by SREBP-2. The protective effect was much stronger for the C vs. T promoter allele. Expression studies confirmed the stimulatory influence of SREBP-2 was significantly stronger for the C promoter. Simvastatin up-regulated promoter activity of the C allele, but had a minor effect on the T allele. Hypercholesterolemic patients homozygous for the C allele showed a significant increase in serum paraoxonase-1 activity and mass during treatment with simvastatin, whereas patients homozygous for the T allele showed no increase.
Conclusions:
The study has delimited the region responsive to transcription factors to a sequence surrounding the C(-107)T polymorphism of the paraoxonase-1 gene, and demonstrated an interaction at this sequence between Sp1 and SREBP-2. SREBP-2 and statin strongly up-regulated the C, but not the T allele. The results suggest a pharmacogenetic interaction between the promoter and simvastatin, which can influence serum paraoxonase in patients.
Related Concept Videos
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
Principles of Pharmacogenetics: Types of Genetic Variants
Pharmacogenomics: Identification of New Drug Targets