The c.-133A > G polymorphism in NPC1L1 gene influences the efficacy of ezetimibe monotherapy on apolipoprotein A1 in hyperlipidemic patients

N. Zsíros, M. Bodor, V. Varga, E. Berta, I. Balogh, I. Seres, G. Paragh, M. Harangi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Niemann-Pick C1-like 1 protein (NPC1L1) plays a critical role in intestinal cholesterol absorption. Previous studies found that the NPC1L1 c.-133A > G SNP, but not other NPC1L1 SNPs, was associated with response to statin treatment and statin-ezetimibe combinations. To date effect of NPC1L1 c.-133A > G SNP on ezetimibe monotherapy has not been studied. Our objective was to examine whether SNP c.-133A > G at the NPC1L1 gene has effects on lipid levels and on the efficacy of 3, 6 and 12 months of 10mg daily ezetimibe monotherapy in hyperlipidemic patients with statin induced adverse effects. One hundred and one type IIa and IIb hyperlipidemic patients (72 females, 29 males; age: 61.23 ± 9.87 ys; BMI: 28.18 ± 4.29 kg/m2) were enrolled. The genotype frequencies were conformed to Hardy-Weinberg equilibrium. We could not find significant differences in initial lipid levels between AA and AG+GG patients. While plasma levels of apolipoprotein A1 (ApoA1) did not significantly decrease after ezetimibe treatment (1.96; 3.39 and 2.74%) in AA patients, a significant elevation in ApoA1 levels has been found after treatment in AG+GG patients (9.15; 8.54 and 13.58%). The effect of NPC1L1 c.-133A > G on the ApoA1 levels was found significant (p <0.05). Efficacy of treatment with ezetimibe on other plasma lipid parameters after 3, 6 or 12 months did not differ significantly. NPC1L1 -133A > G SNP influences the ApoA1 response to ezetimibe monotherapy, therefore, may alter the effect of ezetimibe on the structure and function of the high-density lipoprotein particles.

Original languageEnglish
Pages (from-to)424-429
Number of pages6
JournalPharmazie
Volume69
Issue number6
DOIs
Publication statusPublished - 2014

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Apolipoproteins
Single Nucleotide Polymorphism
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Apolipoprotein A-I
Proteins
Lipids
Intestinal Absorption
HDL Lipoproteins
Ezetimibe
Therapeutics
Cholesterol
Genotype

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

The c.-133A > G polymorphism in NPC1L1 gene influences the efficacy of ezetimibe monotherapy on apolipoprotein A1 in hyperlipidemic patients. / Zsíros, N.; Bodor, M.; Varga, V.; Berta, E.; Balogh, I.; Seres, I.; Paragh, G.; Harangi, M.

In: Pharmazie, Vol. 69, No. 6, 2014, p. 424-429.

Research output: Contribution to journalArticle

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abstract = "Niemann-Pick C1-like 1 protein (NPC1L1) plays a critical role in intestinal cholesterol absorption. Previous studies found that the NPC1L1 c.-133A > G SNP, but not other NPC1L1 SNPs, was associated with response to statin treatment and statin-ezetimibe combinations. To date effect of NPC1L1 c.-133A > G SNP on ezetimibe monotherapy has not been studied. Our objective was to examine whether SNP c.-133A > G at the NPC1L1 gene has effects on lipid levels and on the efficacy of 3, 6 and 12 months of 10mg daily ezetimibe monotherapy in hyperlipidemic patients with statin induced adverse effects. One hundred and one type IIa and IIb hyperlipidemic patients (72 females, 29 males; age: 61.23 ± 9.87 ys; BMI: 28.18 ± 4.29 kg/m2) were enrolled. The genotype frequencies were conformed to Hardy-Weinberg equilibrium. We could not find significant differences in initial lipid levels between AA and AG+GG patients. While plasma levels of apolipoprotein A1 (ApoA1) did not significantly decrease after ezetimibe treatment (1.96; 3.39 and 2.74{\%}) in AA patients, a significant elevation in ApoA1 levels has been found after treatment in AG+GG patients (9.15; 8.54 and 13.58{\%}). The effect of NPC1L1 c.-133A > G on the ApoA1 levels was found significant (p <0.05). Efficacy of treatment with ezetimibe on other plasma lipid parameters after 3, 6 or 12 months did not differ significantly. NPC1L1 -133A > G SNP influences the ApoA1 response to ezetimibe monotherapy, therefore, may alter the effect of ezetimibe on the structure and function of the high-density lipoprotein particles.",
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