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Determinants of variable response to simvastatin treatment: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes

The Pharmacogenomics Journal volume 5, pages 359–364 (2005)Cite this article

Abstract

We investigated the effect of single-nucleotide polymorphisms in sterol regulatory element-binding factors-1a and -2 (SREBF-1a and SREBF-2) and SREBF cleavage-activating protein (SCAP) genes on lipid-lowering response to simvastatin. In all, 146 hypercholesterolemic patients of European descent were prospectively treated with simvastatin 20 mg/day for over 6 months. Of these 99 subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. The mean percentage decrease in plasma total cholesterol (TC) was greater in subject carriers of SCAP 2386G allele compared with those homozygous for 2386A allele (−29.6±13.4 vs −22.1±13.8%, P=0.007). About 61% of the 2386G carriers were above-average responders for TC levels (ΔTC −27.8%), whereas only 29% of 2386A homozygous reached this reduction (P=0.009). Our data suggest that the SCAP 2386A>G gene polymorphism was a significant predictor of TC and triglyceride responses to simvastatin treatment.

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Abbreviations

Apo:

apolipoprotein

CHD:

coronary heart disease

ER:

endoplasmatic reticulum

HDL-C:

high-density lipoprotein cholesterol

LDL-C:

low-density lipoprotein cholesterol

SCAP:

SREBF cleavage-activating protein

SD:

standard deviation

SNPs:

single-nucleotide polymorphisms

SREBF:

sterol regulatory element-binding factor

TC:

total cholesterol

TG:

triglyceride

WD:

triptophane-aspartate

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Acknowledgements

We thank the staff of Centro de Diagnóstico Cardiológico for their assistance. Financial support for this work was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Programa de Apoio a Núcleos de Excelência (PRONEX, Brazil) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil). We are also grateful to the Merck Sharp & Dohme Pharmaceutical Company for providing simvastatin for this project.

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Authors and Affiliations

  1. Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    M Fiegenbaum, F R Silveira & M H Hutz

  2. Centro de Diagnóstico Cardiológico, Porto Alegre, Brazil

    C R Van der Sand, L C Van der Sand, M E W Ferreira & R C Pires

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  1. M Fiegenbaum
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  2. F R Silveira
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  3. C R Van der Sand
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  4. L C Van der Sand
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  7. M H Hutz
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Correspondence to M H Hutz.

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None declared.

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Fiegenbaum, M., Silveira, F., Van der Sand, C. et al. Determinants of variable response to simvastatin treatment: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes. Pharmacogenomics J 5, 359–364 (2005). https://doi.org/10.1038/sj.tpj.6500334

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