Kyle Melin1, Jee-Young Moon2, Qibin Qi2, Dagmar F Hernandez-Suarez3, Jorge Duconge4, Simin Hua2, Sara Gonzalez2, Donglin Zeng5, Robert C Kaplan2,6. 1. Department of Pharmacy Practice, School of Pharmacy, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA. 2. Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. 3. Division of Cardiovascular Medicine, Department of Medicine, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA. 4. Department of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA. 5. Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. 6. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Abstract
PURPOSE: Although clopidogrel is the most widely used oral P2Y12 receptor antagonist, up to 10% of acute coronary syndrome patients treated with clopidogrel will experience a recurrent myocardial infarction and 2-3% will experience stent thrombosis within 1 year. The purpose of this research is to describe the prevalence of pharmacogene variants associated with clopidogrel responsiveness (CYP2C19, B4GALT2, ABCB1, PON1, CES1 and P2RY12) in Hispanic/Latino patients of diverse backgrounds. METHODS: Minor allele frequencies of nine variants from participants of Hispanic Community Health Study/Study of Latinos were compared between subpopulations as well as to continental ancestry references using z-test for independent proportions. RESULTS: MAFs for six out of nine variants differed between Caribbean and Mainland subpopulations (p < 0.05). Compared with European reference group, MAFs of ABCB1, CES1 and PON1 were higher in Hispanic Community Health Study/Study of Latinos, whereas B4GALT2 and CYP2C19*2 and *17 were lower. CONCLUSION: Significant differences in the prevalence of most pharmacogenomic variants related to clopidogrel response provide a foundation to better inform ongoing and future clinical studies of clopidogrel pharmacogenetics in the US Hispanic/Latino populations.
PURPOSE: Although clopidogrel is the most widely used oral P2Y12 receptor antagonist, up to 10% of acute coronary syndromepatients treated with clopidogrel will experience a recurrent myocardial infarction and 2-3% will experience stent thrombosis within 1 year. The purpose of this research is to describe the prevalence of pharmacogene variants associated with clopidogrel responsiveness (CYP2C19, B4GALT2, ABCB1, PON1, CES1 and P2RY12) in Hispanic/Latino patients of diverse backgrounds. METHODS: Minor allele frequencies of nine variants from participants of Hispanic Community Health Study/Study of Latinos were compared between subpopulations as well as to continental ancestry references using z-test for independent proportions. RESULTS: MAFs for six out of nine variants differed between Caribbean and Mainland subpopulations (p < 0.05). Compared with European reference group, MAFs of ABCB1, CES1 and PON1 were higher in Hispanic Community Health Study/Study of Latinos, whereas B4GALT2 and CYP2C19*2 and *17 were lower. CONCLUSION: Significant differences in the prevalence of most pharmacogenomic variants related to clopidogrel response provide a foundation to better inform ongoing and future clinical studies of clopidogrel pharmacogenetics in the US Hispanic/Latino populations.
Authors: Katarzyna Bryc; Christopher Velez; Tatiana Karafet; Andres Moreno-Estrada; Andy Reynolds; Adam Auton; Michael Hammer; Carlos D Bustamante; Harry Ostrer Journal: Proc Natl Acad Sci U S A Date: 2010-05-05 Impact factor: 11.205
Authors: Matthew P Conomos; Cecelia A Laurie; Adrienne M Stilp; Stephanie M Gogarten; Caitlin P McHugh; Sarah C Nelson; Tamar Sofer; Lindsay Fernández-Rhodes; Anne E Justice; Mariaelisa Graff; Kristin L Young; Amanda A Seyerle; Christy L Avery; Kent D Taylor; Jerome I Rotter; Gregory A Talavera; Martha L Daviglus; Sylvia Wassertheil-Smoller; Neil Schneiderman; Gerardo Heiss; Robert C Kaplan; Nora Franceschini; Alex P Reiner; John R Shaffer; R Graham Barr; Kathleen F Kerr; Sharon R Browning; Brian L Browning; Bruce S Weir; M Larissa Avilés-Santa; George J Papanicolaou; Thomas Lumley; Adam A Szpiro; Kari E North; Ken Rice; Timothy A Thornton; Cathy C Laurie Journal: Am J Hum Genet Date: 2016-01-07 Impact factor: 11.025
Authors: Marc S Sabatine; Gavin J Blake; Mark H Drazner; David A Morrow; Benjamin M Scirica; Sabina A Murphy; Carolyn H McCabe; William S Weintraub; C Michael Gibson; Christopher P Cannon Journal: Circulation Date: 2005-03-15 Impact factor: 29.690
Authors: Sharon Cresci; Jeremiah P Depta; Petra A Lenzini; Allie Y Li; David E Lanfear; Michael A Province; John A Spertus; Richard G Bach Journal: Circ Cardiovasc Genet Date: 2014-04-24
Authors: Patrick T O'Gara; Frederick G Kushner; Deborah D Ascheim; Donald E Casey; Mina K Chung; James A de Lemos; Steven M Ettinger; James C Fang; Francis M Fesmire; Barry A Franklin; Christopher B Granger; Harlan M Krumholz; Jane A Linderbaum; David A Morrow; L Kristin Newby; Joseph P Ornato; Narith Ou; Martha J Radford; Jacqueline E Tamis-Holland; Carl L Tommaso; Cynthia M Tracy; Y Joseph Woo; David X Zhao Journal: J Am Coll Cardiol Date: 2012-12-17 Impact factor: 24.094
Authors: Ezra A Amsterdam; Nanette K Wenger; Ralph G Brindis; Donald E Casey; Theodore G Ganiats; David R Holmes; Allan S Jaffe; Hani Jneid; Rosemary F Kelly; Michael C Kontos; Glenn N Levine; Philip R Liebson; Debabrata Mukherjee; Eric D Peterson; Marc S Sabatine; Richard W Smalling; Susan J Zieman Journal: J Am Coll Cardiol Date: 2014-09-23 Impact factor: 24.094
Authors: Ali F Sonel; Chester B Good; Jyotsna Mulgund; Matthew T Roe; W Brian Gibler; Sidney C Smith; Mauricio G Cohen; Charles V Pollack; E Magnus Ohman; Eric D Peterson Journal: Circulation Date: 2005-03-15 Impact factor: 29.690
Authors: Jessica L Mega; Sandra L Close; Stephen D Wiviott; Lei Shen; Joseph R Walker; Tabassome Simon; Elliott M Antman; Eugene Braunwald; Marc S Sabatine Journal: Lancet Date: 2010-10-16 Impact factor: 79.321
Authors: Sherezade Khambatta; Milan Seth; Howard S Rosman; David Share; Herbert D Aronow; Mauro Moscucci; Thomas Lalonde; Simon R Dixon; Hitinder S Gurm Journal: Am Heart J Date: 2013-04-09 Impact factor: 4.749
Authors: Eli I Lev; Kevin P Bliden; Young-Hoon Jeong; Shachi Pandya; Kelly Kang; Christopher Franzese; Udaya S Tantry; Paul A Gurbel Journal: J Am Heart Assoc Date: 2014-10-20 Impact factor: 5.501