ABCB1 C3435T polymorphism and risk of adverse clinical events in clopidogrel treated patients: A meta-analysis

Luo, Man; Li, Jiaoxing; Xu, Xiaowei; Sun, Xunsha; Sheng, Wenli

doi:10.1016/j.thromres.2011.12.003

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Volume 129, Issue 6 , Pages 754-759, June 2012

ABCB1 C3435T polymorphism and risk of adverse clinical events in clopidogrel treated patients: A meta-analysis

Man Luo
- Department of Neurology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
- Department of Neurology, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China
- These three authors have contributed equally to this study, and should be considered as co-first authors.
Jiaoxing Li
- Department of Neurology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
- These three authors have contributed equally to this study, and should be considered as co-first authors.
Xiaowei Xu
- Department of Neurology, Weifang People's Hospital, Shandong 261041, China
- These three authors have contributed equally to this study, and should be considered as co-first authors.
Xunsha Sun
- Department of Neurology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
Wenli Sheng
- Department of Neurology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
- Corresponding author at: Department of Neurology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China. Tel.: +86 20 8733 1089; fax: +86 20 8775 5064.

Received 17 August 2011; received in revised form 14 November 2011; accepted 4 December 2011. published online 03 January 2012.

Abstract

Introduction

The ABCB1 C3435T polymorphism limits oral bioavailability of clopidogrel and may influence prognosis of patients treated with clopidogrel. Several studies have examined the association between the C3435T polymorphism and risk of adverse clinical events in clopidogrel treated patients, but the results were inconsistent. To assess the role of the C3435T polymorphism in the impact on clinical outcomes, a meta-analysis was conducted.

Methods

6 studies with 10,153 subjects were included in this meta-analysis. Fixed- or random-effects model was chosen according to heterogeneity. Publication bias was evaluated by fail-safe numbers.

Results

The association of the C3435T polymorphism with risk of overall recurrent ischemic events in clopidogrel treated patients was not statistically significant for all genetic models (OR=1.13, 95%CI: 0.78–1.64, P=0.51; OR=1.15, 95%CI: 0.99–1.33, P=0.07; OR=1.19, 95%CI: 0.81–1.76, P=0.37). Significant association was identified between the C3435T polymorphism and risk of short-term recurrent ischemic events (OR=1.55, 95% CI: 1.09-2.20, P=0.01; OR=1.41, 95% CI: 1.06-1.87, P=0.02; OR=1.77, 95% CI: 1.19-2.63, P=0.005). No statistically significant association between the C3435T polymorphism and stent thrombosis (OR=0.79, 95% CI: 0.47-1.32, P=0.37) or bleeding (OR=0.98, 95% CI: 0.79-1.21, P=0.82) was identified. The results may be affected by publication bias.

Conclusions

This meta-analysis failed to show an association between the ABCB1 C3435T polymorphism and risk of overall recurrent ischemic events, stent thrombosis or bleeding in clopidogrel treated patients. However, the association between TT homozygotes of the C3435T polymorphism and risk of short-term recurrent ischemic events may exist, but needs more studies to confirm.

Keywords: Clopidogrel, Adverse clinical events, ABCB1, Polymorphism, Meta-analysis