Tingting Wang1,2, Hongjian Li1,2, Fengxia Wang3, Li Sun4, Luhai Yu5. 1. Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, China. 2. Institute of Clinical Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, China. 3. Internal Medicine-Cardiovascular Department, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, Xinjiang, China. 4. Institute of Clinical Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, China. 1161553769@qq.com. 5. Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, China. 125385211@qq.com.
Abstract
BACKGROUND: Acute coronary syndrome (ACS) carries a high mortality in Uygur populations. Percutaneous coronary intervention (PCI) is a safe treatment for patients with ACS. Clopidogrel reduces the risk for recurrent cardiovascular events after PCI; however, its activity is influenced by cytochrome P450 (CYP450), ATP-binding cassette transporter B1 (ABCB1), and paraoxonase-1 (PON1). OBJECTIVES: To assess the effects of genetic polymorphisms CYP2C19*2, *3, *17, ABCB1 C3435T, and PON1 Q192R along with clinical and demographic factors on variations in responses in Uygur patients following PCI. METHODS: We enrolled 281 patients with PCI who were treated with clopidogrel and aspirin for at least 12 months and recorded major adverse cardiovascular events (MACE) or bleeding within 1 year. Approximately, 2 mL of peripheral venous blood samples were used for genotype detection. Binary logistic regression with likelihood ratio forward stepwise analysis and redundancy analysis were carried out to identify factors associated with MACE. We analyzed risk factors including age, body mass index, smoking, hypertension, dyslipidemia, gender, alcohol consumption, diabetes mellitus, carriers of ABCB1 C3435T T allele, carriers of PON1 Q192R A allele, metabolizer phenotype of CYP2C19, number of targeted vessels, and number of stents. RESULTS: The CYP2C19 IMs (OR 3.546, 95% CI 1.972-6.375, P = 0.001), CYP2C19 PMs (OR 7.038, 95% CI 1.658-29.880, P = 0.008), and number of targeted vessels (OR 2.033, 95% CI 1.078-3.648, P = 0.026) were significantly associated with MACE. CONCLUSION: The CYP2C19 IMs, PMs, and the number of targeted vessels are essential factors associated with MACE risk in dual clopidogrel-treated Uygur population with ACS following PCI. These data provide valuable insights into the genetic polymorphisms affecting clopidogrel response among minority groups in China.
BACKGROUND: Acute coronary syndrome (ACS) carries a high mortality in Uygur populations. Percutaneous coronary intervention (PCI) is a safe treatment for patients with ACS. Clopidogrel reduces the risk for recurrent cardiovascular events after PCI; however, its activity is influenced by cytochrome P450 (CYP450), ATP-binding cassette transporter B1 (ABCB1), and paraoxonase-1 (PON1). OBJECTIVES: To assess the effects of genetic polymorphisms CYP2C19*2, *3, *17, ABCB1 C3435T, and PON1 Q192R along with clinical and demographic factors on variations in responses in Uygur patients following PCI. METHODS: We enrolled 281 patients with PCI who were treated with clopidogrel and aspirin for at least 12 months and recorded major adverse cardiovascular events (MACE) or bleeding within 1 year. Approximately, 2 mL of peripheral venous blood samples were used for genotype detection. Binary logistic regression with likelihood ratio forward stepwise analysis and redundancy analysis were carried out to identify factors associated with MACE. We analyzed risk factors including age, body mass index, smoking, hypertension, dyslipidemia, gender, alcohol consumption, diabetes mellitus, carriers of ABCB1 C3435T T allele, carriers of PON1 Q192R A allele, metabolizer phenotype of CYP2C19, number of targeted vessels, and number of stents. RESULTS: The CYP2C19 IMs (OR 3.546, 95% CI 1.972-6.375, P = 0.001), CYP2C19 PMs (OR 7.038, 95% CI 1.658-29.880, P = 0.008), and number of targeted vessels (OR 2.033, 95% CI 1.078-3.648, P = 0.026) were significantly associated with MACE. CONCLUSION: The CYP2C19 IMs, PMs, and the number of targeted vessels are essential factors associated with MACE risk in dual clopidogrel-treated Uygur population with ACS following PCI. These data provide valuable insights into the genetic polymorphisms affecting clopidogrel response among minority groups in China.
Authors: Dragana Stokanovic; Valentina N Nikolic; Sandra S Konstantinovic; Jelena B Zvezdanovic; Jelena Lilic; Svetlana R Apostolovic; Milan Pavlovic; Vladimir S Zivkovic; Tatjana Jevtovic-Stoimenov; Slobodan M Jankovic Journal: Pharmacology Date: 2015-12-23 Impact factor: 2.547
Authors: Betti Giusti; Anna Maria Gori; Rossella Marcucci; Claudia Saracini; Anna Vestrini; Rosanna Abbate Journal: Pharmgenomics Pers Med Date: 2010-04-08