Acta Pharmacologica Sinica (2009) 30: 291-298; doi: 10.1038/aps.2009.14

Acta Pharmacologica Sinica (2009) 30: 291-298; doi: 10.1038/aps.2009.14

Original Article

C-reactive protein polymorphisms and genetic susceptibility to ischemic stroke and hemorrhagic stroke in the Chinese Han population

Qi WANG^1,#, Hu DING^1,#, Jia-rong TANG^1,#, Lan ZHANG¹, Yu-jun XU¹, Jiang-tao YAN¹, Wei WANG¹, Ru-tai HUI²,
Cong-yi WANG³, Dao-wen WANG^1,*

¹The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030; ²Fuwai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, China; ³Center for Biotechnology and Genomic Medicine, Medical College of Georgia, 1120 15th Street, CA4098, Augusta, GA, USA

Aim: The inflammatory marker C-reactive protein (CRP) has been strongly correlated with the risk of cardiovascular disease. Some single-nucleotide polymorphisms (SNPs) have been reported to be associated with serum CRP levels. In this study, we assessed the genetic association between SNPs within the CRP gene and ischemic and hemorrhagic stroke in the Han Chinese population.

Methods: This study comprises 564 ischemic stroke patients, 220 hemorrhagic stroke patients and 564 controls from the ethnic Han Chinese population in Wuhan . Four CRP SNPs, -757A >G (rs3093059), -717A >G (rs2794521), -286C >T>A (rs3091244) and + 2147C >T (rs1205), were genotyped from patients using TaqMan assays.

Results: The A allele frequency for the -717A >G polymorphism was significant higher in controls than in ischemic stroke patients (P=0.037), after adjustment for traditional risk factors (odds ratio 0.28; 95% CI 0.12-0.65; P=0.003), suggesting a protective effect for this allele against ischemic stroke. Haplotype analysis showed that the H3 (G-C-C) haplotype conferred a significantly increased risk of ischemic stroke (odds ratio 1.052, 95% CI 1.001-1.106: P=0.047). Neither CRP genotypes nor haplotypes showed an association with hemorrhagic stroke. However, the frequency for haplotype H5 (A-T-C) was significantly higher in ischemic stroke than hemorrhagic stroke patients (P=0.0003).

Conclusion: These data suggest that the CRP gene -717A allele confers a protective effect against ischemic stroke. Furthermore, the H3 haplotype (G-C-C) is an independent risk marker for ischemic stroke, whereas the H5 haplotype (A-T-C) can be used as a prognostic marker of hemorrhagic stroke.

Keywords: C-reactive protein gene; stroke; genetic polymorphism

This work was supported by grants from National ?63?project (No 2006AA02A406) and ?73?project (No 2007CB512004).

# The first three authors contributed equally to this work.
* Correspondence to Prof Dao-wen WANG, MD, PhD.
E-mail dwwang@tjh.tjmu.edu.cn
Received 2008-12-07 Accepted 2009-01-23

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