Cardiovascular Drugs and the Genetic Response

Dandona, Sonny

doi:10.14797/mdcj-10-1-13

Cited by 8 publications

(4 citation statements)

References 54 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, a reduced transporter activity caused more susceptible to statininduced myotoxicity in the group of patients carrying SLCO1B1 polymorphisms than those without polymorphisms (Sakamoto and Kimura, 2013;Hamann et al, 2013;Ramsey et al, 2014). SLCO1B1*5 has been strongly associated with myopathy among the simvastatin users with an odds ratio (OR) ranging from 4.5 in heterozygotes to 16.9 in homozygotes (Link et al, 2008;Ghatak et al, 2010;Mammen and Amato, 2010;Sirtori et al, 2012;Hu et al, 2012;Rallidis et al, 2012;Sathasivam, 2012;Gong and Kim, 2013;Bhardwaj et al, 2013;Dandona, 2014;Albayda and Christopher-Stine, 2014;Maeda, 2015). Also, SLCO1B1*15 showed over 70% reduction in the transport activity compared with wild type and showed the association with myopathy in patients taking pravastatin and atorvastatin (Ghatak et al, 2010;Sirtori et al, 2012;Gong and Kim, 2013;Shitara et al, 2013;Maeda, 2015).…”

Section: Introductionmentioning

confidence: 99%

Genetic Variations and Frequencies of the Two Functional Single Nucleotide Polymorphisms of SLCO1B1 in the Thai Population

et al. 2020

View full text Add to dashboard Cite

Aim: To investigate the variations and the frequencies of the SLCO1B1 gene in the Thai population. Methods: Collected samples were categorized into five regions of Thailand. DNA samples were genotyped for two variants, c.388A>G and c.521T>C of the SLCO1B1, using TaqMan ® real-time PCR. Results: The minor allele frequencies (MAFs) of two single nucleotide polymorphisms (SNPs) were not significantly different among the five regions. The most frequent haplotype was SLCO1B1*1b (frequency: 0.654), followed by *1a (frequency: 0.217), *15 (frequency: 0.128), and *5 (frequency: 0.001). We observed a similar frequency of OATP1B1 transporter phenotypes compared to other populations. 75.85% of the Thai subjects showed normal OATP1B1 activity, 22.5% showed intermediate OATP1B1 activity, and 1.58% showed low OATP1B1 activity. Conclusion: This study reported the frequencies of the SLCO1B1 variants and the subsequent OATP1B1 activity in a large cohort of Thais that can provide important information for the guidance of personalized drug therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Genetic Variations and Frequencies of the Two Functional Single Nucleotide Polymorphisms of SLCO1B1 in the Thai Population

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Previous studies have demonstrated that carriers of the *1b allele exhibit increased transport activity of pravastatin and decreased plasma concentrations of ezetimibe 19,20 , whereas carriers of the *5 variant show reduced uptake of statins, including pravastatin 26,33 and rifampicin 34 , in hepatocytes, as well as show increased area under the AUC curve for fexofenadine, repaglinide, and irinotecan 21,[23][24][25] . Furthermore, SLCO1B1*5 is strongly associated with myopathy among simvastatin users 1,[35][36][37][38][39][40][41][42][43][44][45] .…”

Section: Discussionmentioning

confidence: 99%

Frequency of functional exonic single-nucleotide polymorphisms and haplotype distribution in the SLCO1B1 gene across genetic ancestry groups in the Qatari population

Dashti

Al-Matrouk²,

Channanath

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Organic anion transporting polypeptides (OATP), which are encoded by SLCO genes, participate in the hepatic elimination of drugs and xenobiotics. SLCO1B1 is an important pharmacogenomic gene (encoding OATP1B1) associated with response to the uptake of endogenous compounds, such as statin and bilirubin. Ethnicity of the patient modulates the response to these drugs; the frequency and haplotype data for SLCO1B1 genetic variants in the Arab population is lacking. Therefore, we determined the frequencies of two well-characterized SLCO1B1 single nucleotide polymorphisms (SNP) and haplotypes that affect the OATP1B1 drugs transportation activity in Qatari population. Genotyping data for two SLCO1B1 SNPs (c.388A > G, c.521 T > C) were extracted from whole exome data of 1050 Qatari individuals, who were divided into three ancestry groups, namely Bedouins, Persians/South Asians, and Africans. By way of using Fisher's exact and Chi-square tests, we evaluated the differences in minor allele frequency (MAF) of the two functional SNPs and haplotype frequencies (HF) among the three ancestry groups. The OATP1B1 phenotypes were assigned according to their function by following the guidelines from the Clinical Pharmacogenetics Implementation Consortium for SLCO1B1 and Simvastatin-Induced Myopathy.The MAF of SLCO1B1:c.388A > G was higher compared to that of SLCO1B1:c.521 T > C in the study cohort. It was significantly high in the African ancestry group compared with the other two groups, whereas SLCO1B1:c.521 T > C was significantly low in the African ancestry group compared with the other two groups. The SLCO1B1 *15 haplotype had the highest HF, followed by *1b, *1a, and *5. Only the SLCO1B1 *5 haplotype showed no significant difference in frequency across the three ancestry groups. Furthermore, we observed that the OATP1B1 normal function phenotype accounted for 58% of the Qatari individuals, the intermediate function phenotype accounted for 35% with significant differences across the ancestry groups, and the low function phenotype accounted for 6% of the total Qatari individuals with a higher trend observed in the Bedouin group.The results indicate that the phenotype frequencies of the OATP1B1 intermediate and low function in the Qatari population appear at the higher end of the frequency range seen worldwide. Thus, a pharmacogenetic screening program for SLCO1B1 variants may be necessary for the Qatari population.

show abstract

“…Statins are a class of medication that reduces the production of cholesterol by inhibiting the enzyme 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase [60]. Seven statins are currently on the market [61]. These are atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin [61].…”

Section: Definitionsmentioning

confidence: 99%

“…Seven statins are currently on the market [61]. These are atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin [61].…”

Section: Definitionsmentioning

confidence: 99%

Pharmacogenetics: An Important Part of Drug Development with A Focus on Its Application

Oates¹,

Lopez²

2018

Int J Biomed Investig

View full text Add to dashboard Cite

Since the human genome project in 2003, the view of personalized medicine to improve diagnosis and cure diseases at the molecular level became more real. Sequencing the human genome brought some benefits in medicine such as early detection of diseases with a genetic predisposition, treating patients with rare diseases, the design of gene therapy and the understanding of pharmacogenetics in the metabolism of drugs. This review explains the concepts of pharmacogenetics, polymorphisms, mutations, variations, and alleles, and how this information has helped us better understand the metabolism of drugs. Multiple resources are presented to promote reducing the gap between scientists, physicians, and patients in understanding the use and benefits of pharmacogenetics. Some of the most common clinical examples of genetic variants and how pharmacogenetics was used to determine treatment options for patients having these variants were discussed. Finally, we evaluated some of the challenges of implementing pharmacogenetics in a clinical setting and proposed actions to be taken to make pharmacogenetics a standard diagnostic tool in personalized medicine.

show abstract

Cardiovascular Drugs and the Genetic Response

Cited by 8 publications

References 54 publications

Genetic Variations and Frequencies of the Two Functional Single Nucleotide Polymorphisms of SLCO1B1 in the Thai Population

Genetic Variations and Frequencies of the Two Functional Single Nucleotide Polymorphisms of SLCO1B1 in the Thai Population

Frequency of functional exonic single-nucleotide polymorphisms and haplotype distribution in the SLCO1B1 gene across genetic ancestry groups in the Qatari population

Pharmacogenetics: An Important Part of Drug Development with A Focus on Its Application

Contact Info

Product

Resources

About