Influence Of POR*28 Polymorphism on Atorvastatin Response in Hyperlipidemic South Indian Population
European Journal of Molecular & Clinical Medicine,
2022, Volume 9, Issue 7, Pages 9430-9437
AbstractContext: Hyperlipidemia is one of the major causes of cardiovascular problems in our population that may even cause mortality among most of the people. Atorvastatin, one of the commonly used statins for hyperlipidemia acts by lowering the total cholesterol and LDL levels in the body. It is metabolized by the enzyme CYP3A4 and CYP3A5 regulated by the POR gene. Presence of nonfunctional allele (POR*28) in POR gene may affect the hypolipidemic activity. Hence we planned our study to find the association of POR*28 genetic polymorphism with lipid lowering effect of atorvastatin in hyperlipidemic patients.
Methods: 57 patients visiting the OPD of general medicine in MGMCRI coming under the inclusion criteria were included for the study. Baseline lipid profile was recorded after which patients were prescribed with 10mg of atorvastatin. Lipid profile was assessed after 4 weeks of treatment, during which 2ml blood was withdrawn for genotyping and patients were assessed for adherence by Morisky medication adherence scale. Medication adherent patients were categorized as responders based on the reduction of LDL by 10% or more and as nonresponders based on the reduction of LDL by less than 10% from the baseline. Genomic DNA was extracted by Qiagen DNA extraction kit and genotyping of POR*28 SNP is done by Realtime PCR using TaqMan genotyping.
Results: The frequency of Extensive metabolizers (EM), Intermediate Metabolizers (IM) and Poor Metabolizers (PM) were 35.29%, 45.10% and 19.61%respectively and they were in Hardy Weinberg Equilibrium. The association between the genotype and clinical response was statistically analyzed using Fischer's exact test and was found to be statistically significant (0.0001). Carriers of POR*28 SNP were found to have lowered lipid lowering effect.
Conclusion: Hence we conclude that the presence of mutant allele, POR*28 affects the antihyperlipidemic activity of statins. However, studies on larger samples are required to extrapolate it.
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