Tejasvita Gaikwad1, Kanjaksha Ghosh1, Shrimati Shetty2. 1. National Institute of Immunohaematology (ICMR), Department of Thrombosis and Haemostasis, 13th Floor, KEM Hospital, Parel, Mumbai, India. 2. National Institute of Immunohaematology (ICMR), Department of Thrombosis and Haemostasis, 13th Floor, KEM Hospital, Parel, Mumbai, India. Electronic address: shrimatishetty@yahoo.com.
Abstract
BACKGROUND: Warfarin is the most widely used anticoagulant all over the world for prevention and treatment of different thrombotic conditions. Polymorphisms in two genes i.e. CYP2C9 (Cytochrome P450 2C9) and VKORC1 (Vitamin K epoxide reductase complex subunit 1) play a major role in warfarin dose variation and its related adverse effects. Different ethnic groups have shown significant differences in dose requirement. METHOD: A systematic electronic search was carried out in PUBMED and ScienceDirect using different key words like, 'warfarin', 'CYP2C9', 'VKORC1', 'pharmacokinetics', 'metabolites' and 'genetic'. Till date, data from 15 Asian countries for CYP2C9 genotypes and 14 Asian countries for VKORC1 genotypes could be retrieved. RESULTS: Approximately 90% of the subjects from East Asian countries were found to be carriers for VKORC1 1639 'A' or 1173 'T' allele (associated with low dose warfarin), while the prevalence of these alleles in the rest of the Asian countries (except Iran) i.e. South, South East, West and Central Asia ranged between 14 and 80%. Interestingly, an increase in carrier rate for CYP2C9 2 or 3 alleles was observed as we move from East to West Asia and an opposite trend was observed with VKORC1 1639 'A' or 1173 'T' alleles. Countries like Iran, Oman, India and Russia showed a drastic variation in the distribution pattern of these genotypes from that of the neighboring countries. CONCLUSION: The analysis further highlights the importance of genotype based warfarin dosing in each country. Since many Asian countries are still underrepresented in pharmacogenomic research, addition of data from these underrepresented countries will be beneficial for safe warfarin dosing in these patients.
BACKGROUND:Warfarin is the most widely used anticoagulant all over the world for prevention and treatment of different thrombotic conditions. Polymorphisms in two genes i.e. CYP2C9 (Cytochrome P450 2C9) and VKORC1 (Vitamin K epoxide reductase complex subunit 1) play a major role in warfarin dose variation and its related adverse effects. Different ethnic groups have shown significant differences in dose requirement. METHOD: A systematic electronic search was carried out in PUBMED and ScienceDirect using different key words like, 'warfarin', 'CYP2C9', 'VKORC1', 'pharmacokinetics', 'metabolites' and 'genetic'. Till date, data from 15 Asian countries for CYP2C9 genotypes and 14 Asian countries for VKORC1 genotypes could be retrieved. RESULTS: Approximately 90% of the subjects from East Asian countries were found to be carriers for VKORC1 1639 'A' or 1173 'T' allele (associated with low dose warfarin), while the prevalence of these alleles in the rest of the Asian countries (except Iran) i.e. South, South East, West and Central Asia ranged between 14 and 80%. Interestingly, an increase in carrier rate for CYP2C9 2 or 3 alleles was observed as we move from East to West Asia and an opposite trend was observed with VKORC1 1639 'A' or 1173 'T' alleles. Countries like Iran, Oman, India and Russia showed a drastic variation in the distribution pattern of these genotypes from that of the neighboring countries. CONCLUSION: The analysis further highlights the importance of genotype based warfarin dosing in each country. Since many Asian countries are still underrepresented in pharmacogenomic research, addition of data from these underrepresented countries will be beneficial for safe warfarin dosing in these patients.
Authors: Maryam H Alrashid; Ahmad Al-Serri; Salem H Alshemmari; Philip Koshi; Suzanne A Al-Bustan Journal: Mol Diagn Ther Date: 2016-04 Impact factor: 4.074
Authors: Keun Sik Hong; Yang Ki Kim; Hee Joon Bae; Hyo Suk Nam; Sun U Kwon; Oh Young Bang; Jae Kwan Cha; Byung Woo Yoon; Joung Ho Rha; Byung Chul Lee; Jong Moo Park; Man Seok Park; Jun Lee; Jay Chol Choi; Dong Eog Kim; Kyung Bok Lee; Tai Hwan Park; Ji Sung Lee; Seong Eun Kim; Juneyoung Lee Journal: J Clin Neurol Date: 2017-07 Impact factor: 3.077