Online ISSN: 2515-8260

Keywords : Cytochrome P450 oxidoreductase

CYP2D6*4 Polymorphism on Tramadol Analgesia in Acute Osteoarthritic Knee Pain in South Indian Population

Sudar Codi. R, Samuel Kirubakaran.D, Aarthi M, Manoharan M , Adithan C

European Journal of Molecular & Clinical Medicine, 2022, Volume 9, Issue 7, Pages 9416-9422

Context: Inadequate pain relief is commonly experienced by patients on pain medications for chronic diseases. Tramadol, an opioid analgesic is metabolized by CYP2D6 to active metabolite, responsible for analgesic activity. The presence of non-functional CYP2D6*4 allele may affect pain relief. Hence the aim of our study is to investigate the influence of CYP2D6*4 on the analgesic effect of tramadol in acute osteoarthritic knee pain
Methods and Material: Seventy six patients visiting the orthopaedicians of MGMCRI with acute osteoarthritic knee pain and 49 fulfilling the study criteria were included. Pain intensity was recorded using visual analogue scale (VAS) at baseline and after 5 days. 2mL blood was collected for genotyping. Patients received Tab.Tramadol 50mg BD for five days. Patients were categorized as responders if patients experience 50% or more pain relief from the baseline. Genomic DNA was extracted using Qiagen Kit. Genotyping was performed using TaqMan SNP Assay on Real Time system.  Chi Square test was used to study the association between metabolizer phenotype determined by CYP2D6*4 and pain relief.
Results: The frequency of Extensive metabolizers(EM), Intermediate Metabolizers(IM) and Poor Metabolizers(PM) were 90.6%, 5.3% and 4% respectively. The allele was in Hardy Weinberg Equilibrium (p=0.1062). There was a statistically significant association between the metabolizer phenotype and pain relief (p=0.0349). There were significantly more number of responders with EM phenotype.
Conclusion: The genotype of CYP2D6*4 non-functional allele influences the analgesic effect of tramadol. However, studies on larger samples are required to extrapolate it.

Influence Of POR*28 Polymorphism on Atorvastatin Response in Hyperlipidemic South Indian Population

Shagana. S, Sudar Codi. R, Manimekalai.K

European Journal of Molecular & Clinical Medicine, 2022, Volume 9, Issue 7, Pages 9430-9437

Context: 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.