Pharmacogenetic determinants of warfarin in the Indian population.

Pharmacological Reports : PR
Shaik Mohammad NaushadSalman A Alrokayan

Abstract

Several studies optimized the warfarin dose based on CYP2C9*2, CYP2C9*3, VKORC1 -1639 G > A, CYP4F2 V433M. But, the information on the rare variants is lacking. In this study, we have explored the prevalence of common and rare pharmacogenetic determinants of warfarin and determined their damaging nature. We have analyzed 2000 healthy adults using the Infinium global screening array (GSA) for 15 pharmacogenetic determinants of warfarin. In addition, we have elucidated the impact of these variants on protein function, stability, dynamics, evolutionary preservation, and ligand binding propensity. The GSA Analysis has revealed that CYP4F2 V433M (MAF: 39.425%), VKORC1 -1639 G > A (MAF: 20.5%), CYP2C9*3 (MAF:9.925%), and CYP2C9*2 (MAF:4.575%) are common, while CYP2C9*14 (MAF: 1.475%), CYP2C9*4 (0.175%), CYP2C9*5 (0.125%), and CYP2C9*11 (0.125%) are rare. Position-specific evolutionary preservation (PSEP) analysis has revealed that CYP2C9*4 is possibly damaging, while CYP2C9*5, CYP2C9*11, and CYP2C9*14 are probably damaging. CYP2C9*4 has high thermolability (-10.14 kcal/mol). Among the rare CYP2C9 variants, CYP2C9*4 and CYP2C9*11 exert destabilizing effects and may have increased molecular flexibility, while CYP2C9*5 and CYP2C9*14 exe...Continue Reading

References

Sep 17, 2004·Clinical Pharmacology and Therapeutics·Feng ZhaoSoo Chin Lee
Jun 23, 2005·Pharmacogenetics and Genomics·Guoying TaiAllan E Rettie
Oct 19, 2006·Human Genetics·Mia WadeliusPanos Deloukas
Feb 29, 2008·Clinical Pharmacology and Therapeutics·B F GageH L McLeod
Jun 11, 2008·European Journal of Clinical Pharmacology·G Oner OzgonJ A Johnson
Feb 21, 2009·The New England Journal of Medicine·UNKNOWN International Warfarin Pharmacogenetics ConsortiumJ A Johnson
Mar 2, 2011·The Pharmacogenomics Journal·A PavaniV K Kutala
Jun 12, 2013·The Pharmacogenomics Journal·Y NiinumaM Hiratsuka
Sep 11, 2013·European Journal of Clinical Pharmacology·Dhakchinamoorthi Krishna KumarChandrasekaran Adithan
Jun 24, 2014·Pharmacogenomics·Yee Ming LeeLarisa H Cavallari
Jul 8, 2017·Pharmacogenomics·Alison Lh QuinnJames C Lee
Feb 1, 2020·Clinical and Translational Science·Lingxin ZhangRichard Weinshilboum
Sep 17, 2020·Pharmacological Reports : PR·Shaik Mohammad NaushadSalman A Alrokayan
Oct 27, 2020·The Journal of Gene Medicine·Shaik Mohammad NaushadVijay Kumar Kutala

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