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Genetic variants of ABCB1 may affect intestinal absorption of clopidogrel bisulfate. However, it is unclear whether ABCB1 polymorphisms are associated with clopidogrel efficacy for minor ischemic stroke or transient ischemic attack (TIA).
To investigate the association between ABCB1 polymorphisms and clopidogrel efficacy for minor stroke or TIA.
Design, Setting, and Participants
In this prespecified secondary analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) randomized clinical trial, 3010 patients with minor stroke or TIA at 73 sites in China with experience in conducting genetic studies were included from October 1, 2009, to July 30, 2012. The analysis was conducted on March 20, 2018. Four single-nucleotide polymorphisms (ABCB1 -154T>C [rs4148727], ABCB1 3435C>T [rs1045642], CYP2C19*2 [681G>A, rs4244285], and CYP2C19*3 [636G>A, rs4986893]) were genotyped among 2836 patients treated with clopidogrel plus aspirin (n = 1414) or aspirin alone (n = 1422). The association of ABCB1 genetic variants (-154 TC/CC and 3435 CT/TT) with clopidogrel efficacy was evaluated in the context of CYP2C19 status, another gene associated with clopidogrel efficacy.
Patients in the CHANCE trial were randomized to treatment with clopidogrel combined with aspirin or to aspirin alone.
Main Outcomes and Measures
Primary efficacy outcome was stroke recurrence after 3 months. The safety outcome was any bleeding risk after 3 months.
Among 2836 patients, the median age was 61.8 years (interquartile range, 54.4-71.1 years) and 1887 patients (66.5%) were male. A total of 2146 (75.7%) patients were carriers of ABCB1 -154 TC/CC (570 [20.1%]) or 3435 CT/TT (1851 [65.3%]) genotype. Clopidogrel plus aspirin treatment was associated with reduced risk of new stroke in patients with ABCB1 -154 TT and 3435 CC genotype (hazard ratio [HR], 0.43; 95% CI, 0.26-0.71) but not in those with ABCB1 -154 TC/CC or 3435 CT/TT genotype (HR, 0.78; 95% CI, 0.60-1.03) compared with aspirin (P = .04 for interaction). A combined association of ABCB1 and CYP2C19 polymorphisms with new stroke was observed. The risk of bleeding for clopidogrel plus aspirin treatment was not associated with the ABCB1 genotypes (2.3% and 1.3% vs 1.9% and 2.2%; P = .25 for interaction in patients with or without ABCB1 -154 TC/CC or 3435 CT/TT genotype)
Conclusions and Relevance
The ABCB1 polymorphism was associated with the reduced efficacy of clopidogrel plus aspirin treatment compared with aspirin among patients with minor ischemic stroke or TIA. Genetic polymorphism of ABCB1 should be considered when prescribing clopidogrel for these patients.
ClinicalTrials.gov identifier: NCT00979589
Question Are ABCB1 genetic variants associated with the efficacy of clopidogrel bisulfate for minor stroke or transient ischemic attack? Findings In this secondary analysis of a randomized clinical trial that included 2836 adults, clopidogrel plus aspirin was associated with a significant reduction in the risk of new stroke in patients with ABCB1 -154 TT and 3435 CC genotype but not in those with ABCB1 -154 TC/CC or 3435 CT/TT genotype compared with aspirin alone. Meaning ABCB1 genetic variants may be associated with the efficacy of clopidogrel for treatment of minor stroke or transient ischemic attack
Association Between ABCB1 Polymorphisms and Outcomes of Clopidogrel Treatment in Patients With Minor Stroke or Transient Ischemic Attack Secondary Analysis of a Randomized Clinical Trial
Yuesong Pan, PhD,1,2,3,4 Weiqi Chen, MD, PhD,1,2,3,4 Yilong Wang, MD, PhD,1,2,3,4 Hao Li, PhD,1,2,3,4 S. Claiborne Johnston, MD, PhD,5 Tabassome Simon, MD, PhD,6,7,8 Xingquan Zhao, MD, PhD,1,2,3,4 Liping Liu, MD, PhD,1,2,3,4 David Wang, DO,9,10 Xia Meng, MD, PhD,1,2,3,4 and Yongjun Wang, MDcorresponding author1,2,3,4, for the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) Investigators
The pharmacogenomics study has been widely used for the study of very important pharmacogenetic (VIP) variants among different ethnic groups. However, there is little known about the pharmacogenomics information regarding Bai family. Our study aimed to screen the polymorphism of the VIP gene in Bai nationality.
We genotyped 81 VIP variants (selected from the PharmGKB database) in the Bai population and then compared them to the other 11 major HapMap populations by chi?square test, structure and F?statistics (Fst) analysis.
Our results indicated that rs20417 (PTGS2), rs4148323 (UGT1A), and rs1131596 (SLC19A1) were most different in Bai compared with most of the 11 populations from the HapMap data set. Furthermore, population structure and F?statistics (Fst) analysis also demonstrated that the Bai population has the closest genetic relationship with Han Chinese in Beijing, China (CHB), followed by Japanese in Tokyo, Japan (JPT), and the farthest population from the Yoruba in Ibadan, Nigeria (YRI).
Our study not only presented the genotype frequency difference between the selected population of the Bai population and the other 11 populations, but also showed that the Bai population is most similar to the CHB populations, followed by JPT. These findings would contribute to the development of individualized medicine for the Bai population.
bai ethnic group, genetic polymorphisms, individualized medicine, pharmacogenomics, VIP variants
Genetic polymorphisms analysis of pharmacogenomic VIP variants in Bai ethnic group from China
Wanlu Chen, 1 Heng Ding, 2 Yujing Cheng, 1 Qi Li, 1 Run Dai, 1 Xin Yang, 1 and Chan Zhangcorresponding author 1
Population with malignancy is growing worldwide; however, its tuberculosis (TB) burden including remains unclear regarding incidence, mortality, and relapse. We retrieved information and identified patients with malignancy and TB between 2000 and 2015 from the Taiwanese National Health Insurance reimbursement datasets, Taiwan cancer registry and death registration. We analyzed the incidence of new TB in patients with malignancy and their mortality as well as TB recurrence. During study period, we reviewed 1,105,009 patients after exclusion and among them, 19,906 had newly diagnosed TB. The TB incidence in cancer patients divided all TB events increased annually, from 3% in 2000 to 13% in 2015. The standard incidence rates (SIR) were highest in cancer of respiratory tract (5.45), hematology (3.70) and then head and neck area (2.58). The mortality directly due to TB was defined as 0.83% and all-cause mortality were approximately 10.5% at 3 months and 20.56% at 12 months. After completing TB treatment, recurrence was diagnosed in 626 (3.14%), and 1001 (5.03%) patients within the first and the first two years, respectively. In conclusion, the incidence of TB in patients with malignancy increase yearly as well as its proportion within overall cases. The twelve-month all-cause mortality during TB and the two-year recurrence are as high as 20.56% and 5.03%, respectively. It indicates the importance of this population in future TB control, especially for those with malignancy of respiratory tract, and hematology as well as head and neck area.
Subject terms: Epidemiology, Tuberculosis
The burdens of tuberculosis on patients with malignancy: incidence, mortality and relapse
Chin-Chung Shu,#1,2 Kuang-Ming Liao,#3 Yi-Chen Chen,4 Jhi-Joung Wang,4,5 and Chung-Han Hocorresponding author4,6