Genetic polymorphisms as predictive markers for statin therapy: a route to improved cardiovascular patient outcomes?

Kansu, Bengi; Lang, Derek

doi:10.1093/biohorizons/hzx010

Cited by 3 publications

(2 citation statements)

References 60 publications

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“…During recent years, genetic variations have been studied with respect to the individual differences in response to statins treatment, both in terms of LDL‐C‐lowering and clinical outcomes . Some polymorphisms of candidate genes have been reported to be associated with the adverse reactions of statins …”

Section: What Is Known and Objectivementioning

confidence: 99%

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: What Is Known and Objectivementioning

confidence: 99%

Pharmacogenetics of statins treatment: Efficacy and safety

Guan

et al. 2019

J Clin Pharm Ther

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“…Individual patient genotype is found to have role in controlling responses to drug and the individual genetic polymorphism can influence response to statins. 13 Polymorphism in ABCA1 gene is associated with various lipid transport defects and wide-ranging HDL deficiency. 14 Various single nucleotide polymorphisms (SNPs) of ABCA1 are found to be associated with plasma lipid and susceptibility to coronary artery disease (CAD).…”

Section: Introductionmentioning

confidence: 99%

Effect of ABCA1-R219K Polymorphism in Serum Lipid Parameters in Patients under Statin Therapy Visiting Tertiary Cardiac Center of Nepal

et al. 2023

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Introduction ATP-binding cassette transporter A1 (ABCA1) encoded by ABCA1 gene is one of the important protein involved in lipid metabolism. The effect of statin therapy on dyslipidemia varies among individuals and it may be due to different genetic polymorphism. The R219K polymorphism of ABCA1 gene is found to have a significant role in the response of statin. Objective This study was designed to evaluate the effect of R219K polymorphism in lipid-lowering action of statin in patients with dyslipidemia. Material and Methods This study was conducted in 88 patients. Blood samples were taken from patients before and at the end of 3 months of statin use and were analyzed for lipid profile. Whole blood was analyzed for R219K Polymorphism using polymerase chain reaction-restriction fragment length polymorphism. Results R219K polymorphism was associated with significant percentage reduction of serum triglyceride/high-density lipoprotein (TG/HDL) ratio and total cholesterol/high-density lipoprotein (TC/HDL) ratio in atorvastatin users. However, there was no significant association of polymorphism with change in serum TC, HDL-C, LDL-C, TG, and very low-density lipoprotein (VLDL). Among KK genotype individuals, value of TG, VLDL, TG/HDL, and TC/HDL were significantly lower than in RR genotypes. Also, TG/HDL and TC/HDL were significantly lower in RK genotype than in RR. Treatment of dyslipidemia with statin was found to be comparatively better in patients having the genotypes KK and RK. Conclusion Our study demonstrated association of R219K polymorphism with the significant reduction of TG/HDL and TC/HDL and particularly the KK genotype was associated with significant improvement of lipid parameters following atorvastatin treatment.

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Gender Differences in Response to Statin Therapy in Ischemic Stroke Patients With SLCO1B1 388A>G Polymorphism: A Clinical Study

Sabokbar,

Sharifipour,

Zamanlu

et al. 2023

Biomed Res Bull

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Background: Statins are widely used for the medical management of vascular conditions, including ischemic stroke. However, genetic factors and polymorphisms, including SLCO1B1 388A>G single-nucleotide polymorphism (SNP), have shown significant effects in response to statin therapy. To the best of our knowledge, gender-gene interaction in response to statin therapy, affected by the SLCO1B1 388 A>G SNP, has not been investigated yet. The current study describes the therapeutic outcomes of this variation in terms of clinical evaluations and laboratory parameters. Methods: Seventy patients diagnosed with acute ischemic stroke were recruited for this study. Blood samples were collected. The SLCO1B1 388A>G gene was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method, and the three possible polymorphisms (388GG, 388GA, and 388AA) were detected accordingly. Statin treatment was prescribed at a dose of 40 mg of Atorvastatin or 20 mg of Rosuvastatin daily. Laboratory assessments, including a lipid profile, liver function tests, and lactate dehydrogenase, as well as clinical evaluations, including scores of stroke severity, were obtained at baseline and after a three-month follow-up. Results: Iranian ischemic stroke patients showed all three possible polymorphisms, including 30 patients with AA, 28 patients with AG, and 12 patients with GG. Significant SNP variations and gender-gene interactions for most measures of the lipid profile and some clinical trends were found in such a manner that the GG genotype was associated with relevant resistance to statin treatment, while the AA genotype, particularly in male patients, was associated with more response to statin treatment. Conclusion: This investigation adds influential gender differences to the previously reported SLCO1B1 388A>G SNP-induced variations of statin therapeutic response in stroke patients.

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Genetic polymorphisms as predictive markers for statin therapy: a route to improved cardiovascular patient outcomes?

Cited by 3 publications

References 60 publications

Pharmacogenetics of statins treatment: Efficacy and safety

Pharmacogenetics of statins treatment: Efficacy and safety

Effect of ABCA1-R219K Polymorphism in Serum Lipid Parameters in Patients under Statin Therapy Visiting Tertiary Cardiac Center of Nepal

Gender Differences in Response to Statin Therapy in Ischemic Stroke Patients With SLCO1B1 388A>G Polymorphism: A Clinical Study

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