The ABCB1 2677G&gt;T/A polymorphism is associated with baseline blood HDL-cholesterol levels in newly diagnosed hyperlipidemic patients

Agapakis, Dimitris; Panderi, Athanasia; Gbandi, Emma; Savopoulos, Christos; Kouvelas, Dimitrios; Hatzitolios, Apostolos; Goulas, A.

doi:10.1016/j.hjc.2017.01.023

Cited by 4 publications

(7 citation statements)

References 17 publications

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“…Comparing with patients with 2677 T/A allele, those with 2677 G allele have a lower effluent activity from hepatocyte to bile and a higher hepatic concentration, leading to the accumulation of atorvastatin and inducing hepatotoxicity . Besides, ABCB1 2677G>T/A polymorphism was also shown to be associated with baseline blood HDL‐cholesterol levels in Greek hyperlipidemic patients …”

Section: Resultsmentioning

confidence: 98%

Pharmacogenetics of statins treatment: Efficacy and safety

Guan

et al. 2019

J Clin Pharm Ther

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What is known and objective: Statins are widely used worldwide in the prevention and treatment of coronary atherosclerotic heart disease and ischaemic stroke.However, in clinical application, statins have shown great individual differences in terms of the efficacy and safety, some of which are related to genetic factors. The purpose of this article was to summarize the recent advances about the correlation between gene polymorphisms and the efficacy/safety of statins. Methods:We searched the databases including PharmGKB and PubMed (published before June 2019) using the keywords such as 'statin', 'gene polymorphism' and 'SNP' and obtained more than 100 articles. In this review, we described the clinical studies of genetic variants associated with both the efficacy and adverse reactions of statins.We also clarified the importance of taking pharmacogenetic variation into account to improve the clinical application of statins. Results and discussion:The available data were collected and analysed to present the polymorphisms of candidate genes encoding the most promising proteins including SLCO1B1 (encoding uptake transporters); ABCB1, ABCC2, ABCG2 (encoding effluent transporter); APOE, APOA5 (encoding apolipoprotein); genes encoding cytochrome P450 enzyme system; KIF6, HMGCR, LDLR, LPA, PCSK9, COQ2, CETP, etc These genes were proved to be related to the pharmacodynamics and pharmacokinetics of statins, thus affecting the efficacy and safety. What is new and conclusion:In this paper, the correlation between gene polymorphisms and the efficacy/safety of statins was summarized. The authors reached a consensus that the variants of the genes encoding uptake and effluent transporters have the most effect on the efficacy/safety of statins. It pointed out that it is desirable to do genetic testing of these transporter genes to reduce the incidence of myopathy or to achieve better outcomes before patients use statins, especially in the regions with high frequency of risk allele. K E Y W O R D S cytochrome P450, gene polymorphism, pharmacogenetics, statins, transporter | 859 GUAN et Al.

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Section: Resultsmentioning

confidence: 98%

Pharmacogenetics of statins treatment: Efficacy and safety

Guan

et al. 2019

J Clin Pharm Ther

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“…Determination of FAs was performed in blood samples of 62 hyperlipidemic patients and 42 normolipidemic controls, constituting representative subgroups in terms of ABCB1 G2677T [ 19 ] and PNPLA3 I148M genotype distribution- of the original groups. The original selection was based on known ABCB1 G2677T genotypes; PNPLA3 I148M genotyping failed to produce unequivocal results for one hyperlipidemic patient and two normolipidemic controls.…”

Section: Resultsmentioning

confidence: 99%

“…Amplification conditions were: 5 min at 95 • C, followed by 37 cycles of 30 s at 95 • C, 30 s at 58 • C, and 30 s at 72 • C, and a final extension step of 7 min at 72 • C. The PCR mixture was then treated overnight with FokI (SibEnzyme, Academtown, Siberia, Russia) at 37 • C; the enzyme digests in presence of the C allele (sense strand) to produce 99 and 58 bp fragments, but not in presence of the G allele (sense strand) to leave the 157 fragment uncut. Genotyping data for rs2032582were retrieved from work previously accomplished in our laboratory [19,27].…”

Section: Genotypingmentioning

confidence: 99%

“…Moreover, diet restriction was shown to induce a very strong up-regulation of the ABCB1a gene (one of the two mice orthologs of the human ABCB1 gene) in mice [ 17 ] and, more importantly, Pgp knock-out mice developed obesity, hepatic steatosis and increased liver TGs [ 18 ]. Common polymorphisms of the ABCB1 gene have been associated in the past with serum total cholesterol and/or lipoprotein cholesterol levels [ 19 ], but, as in the case of PNPLA3 gene, the effect of such polymorphisms on individual FA concentrations in human serum remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

“…Determination of individual FAs and exploration of their profiles has been assisted greatly by the development of lipid analysis methodologies. Here, a FA profiling method was applied to provide an insight in the composition of blood samples from a subset of previously characterized hyperlipidemic patients and normolipidemic controls [ 19 ]. The applied method provides reliable quantitative results by the indirect determination of FAs’ more volatile methyl ester derivatives (FA methyl esters, FAMEs) by gas chromatography and flame ionization detection (GC-FID).…”

Section: Introductionmentioning

confidence: 99%

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A Study of Blood Fatty Acids Profile in Hyperlipidemic and Normolipidemic Subjects in Association with Common PNPLA3 and ABCB1 Polymorphisms

et al. 2021

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Adiponutrin (patatin-like phospholipase domain-containing 3; PNPLA3), encoded in humans by the PNPLA3 gene, is a protein associated with lipid droplet and endoplasmic reticulum membranes, where it is apparently involved in fatty acid redistribution between triglycerides and phospholipids. A common polymorphism of PNPLA3 (I148M, rs738409), linked to increased PNPLA3 presence on lipid droplets, is a strong genetic determinant of non-alcoholic fatty liver disease (NAFLD) and of its progression. P-glycoprotein (Pgp, MDR1, ABCB1), encoded by the ABCB1 gene, is another membrane protein implicated in lipid homeostasis and steatosis. In the past, common ABCB1 polymorphisms have been associated with the distribution of serum lipids but not with fatty acids (FA) profiles. Similarly, data on the effect of PNPLA3 I148M polymorphism on blood FAs are scarce. In this study, a gas chromatography-flame ionization detection (GC-FID) method was optimized, allowing us to analyze twenty FAs (C14: 0, C15: 0, C15: 1, C16: 0, C16: 1, C17: 0, C17: 1, C18: 0, C18: 1cis, C18: 2cis, C20: 0, C20: 1n9, C20: 2, C20: 3n6, C20: 4n6, C20: 5, C23: 0, C24: 0 C24: 1 and C22: 6) in whole blood, based on the indirect determination of the fatty acids methyl esters (FAMES), in 62 hyperlipidemic patients and 42 normolipidemic controls. FA concentrations were then compared between the different genotypes of the rs738409 and rs2032582 (ABCB1 G2677T) polymorphisms, within and between the hyperlipidemic and normolipidemic groups. The rs738409 polymorphism appears to exert a significant effect on the distribution of blood fatty acids, in a lipidemic and fatty acid saturation state-depending manner. The effect of rs2032582 was less pronounced, but the polymorphism did appear to affect the relative distribution of blood fatty acids between hyperlipidemic patients and normolipidemic controls.

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