Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population

Kadam, Prajakta; Ashavaid, Tester F.; Ponde, Chandrashekhar K.; Rajani, Rajesh

doi:10.1111/jcpt.12369

Cited by 31 publications

(29 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Conversely, the association of rs4149056 with myopathy has been less compelling for other statins [31]. The impact of rs2306283 polymorphism on the efficacy of statins has been reported, such as pravastatin [31,32], atorvastatin [33][34][35][36], and pitavastatin [37]. However, no report regarding the correlation of rs2306283 polymorphism and simvastatin-induced adverse reaction was published until now.…”

Section: Discussionmentioning

confidence: 99%

Untitled

2019

Drug Res (Stuttg)

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Untitled

2019

Drug Res (Stuttg)

View full text Add to dashboard Cite

“…Only in nine of these 64 publications a positive implementation advice was given. As multiple authors also discuss (Ong et al, 2012 ; Santos et al, 2012 ; Ferrari et al, 2014 ; Kadam et al, 2016 ) this illustrates a lack of adequate measures of effect to conclude on implementation for clinical practice: arguments for or against the eligibility of PGx for statins cannot sufficiently be substantiated. Often the arguments put forward, are genotype-phenotype associations, and do not focus on broader implications for clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Review of the Reported Measures of Clinical Validity and Clinical Utility as Arguments for the Implementation of Pharmacogenetic Testing: A Case Study of Statin-Induced Muscle Toxicity

et al. 2017

View full text Add to dashboard Cite

Advances from pharmacogenetics (PGx) have not been implemented into health care to the expected extent. One gap that will be addressed in this study is a lack of reporting on clinical validity and clinical utility of PGx-tests. A systematic review of current reporting in scientific literature was conducted on publications addressing PGx in the context of statins and muscle toxicity. Eighty-nine publications were included and information was selected on reported measures of effect, arguments, and accompanying conclusions. Most authors report associations to quantify the relationship between a genetic variation an outcome, such as adverse drug responses. Conclusions on the implementation of a PGx-test are generally based on these associations, without explicit mention of other measures relevant to evaluate the test's clinical validity and clinical utility. To gain insight in the clinical impact and select useful tests, additional outcomes are needed to estimate the clinical validity and utility, such as cost-effectiveness.

show abstract

“…This variation has been associated with polymorphisms in genes encoding drug metabolizing enzymes and transporters (34). However, differences in allele frequencies and their effect on quantitative parameters including cholesterol levels, arterial pressure and pharmacokinetic parameters, and associations of genotypes with drug metabolism and response have been documented across various populations (7,33,35,36).…”

Section: Discussionmentioning

confidence: 99%

Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population

et al. 2017

View full text Add to dashboard Cite

Abstract. Discrepancies in the response to drugs are partially due to polymorphisms in genes involved in drug metabolism and transport. The frequency, pattern and impact of these polymorphisms vary among populations. In the present study, the pharmacokinetics and pharmacogenetics of atorvastatin (ATV) in a Mexican population were investigated. The study cohort exhibited differing ATV metabolizing phenotypes, and in subsequent allelic discrimination assays, single nucleotide polymorphisms in the angiotensinogen, angiotensin II type 1 receptor (AGTR1) and bradykinin B2 receptor (BDKRB2) genes were genotyped and their effects on the pharmacokinetic parameters of ATV were assessed. Additionally, association studies were performed to test for a correlation between metabolizing phenotypes and genetic variants. It was observed that carriers of the genotypes A/C and C/T in AGTR1 and BDKRB2 had higher area under the plasma concentration-time curve values from time 0 to the time of the last measurement and from time 0 extrapolated to infinity, and lower values of clearance of the fraction dose absorbed compared with homozygous carriers (P<0.05). Only the C/C genotype of BDKRB2 was associated with the fast metabolizer phenotype. These data suggest that AGTR1 and BDKRB2 are involved in ATV pharmacokinetics; a novel finding that requires confirmation in further studies.

show abstract

Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population

Abstract: The variable response to atorvastatin therapy in terms of LDL-cholesterol lowering due to genetic variations in CYP7A1, CYP3A4, SLCO1B1 and ABCB1 is a promising finding. Further validation in large Indian cohorts is required before it can be assessed for clinical utility.

Cited by 31 publications

References 26 publications

Untitled

Untitled

Review of the Reported Measures of Clinical Validity and Clinical Utility as Arguments for the Implementation of Pharmacogenetic Testing: A Case Study of Statin-Induced Muscle Toxicity

Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population

Contact Info

Product

Resources

About