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Pai-1 Gene Variants and COC Use Are Associated with Stroke Risk: A Case-Control Study in the Han Chinese Women

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Abstract

Genetic variants of plasminogen activator inhibitor type 1 (PAI-1) gene have been suggested to influence the PAI-1 transcription activity and PAI-1 levels as well as might be involved in the pathophysiology of stroke. The aims of this study are to investigate whether the polymorphisms at the PAI-1 gene are associated with the risk of stroke and to explore the combined effects of PAI-1 variants and combined oral contraceptive (COC) use for stroke risk. We conducted a nested case-control study using 453 first-ever female stroke cases and 919 age- and region-matched controls that were recruited from our prospective surveillance cohort. SNP rs1799889 was genotyped by allele-specific polymerase chain reaction (PCR), and SNPs rs7242 and rs2227631 were detected by the TaqMan SNP genotyping assay. We identified that rs1799889 5G allele conferred a protective effect against ischemic stroke while 4G allele conferred an increased risk of ischemic stroke. But we failed to suggest associations of rs7242 and rs2227631. COC users had a 1.31-fold (OR = 1.31, 95 % CI = 1.01–1.71) increased risk of stroke compared with the non-users. Furthermore, COC users with rs1799889 4G5G/5G5G genotype had a decreased risk of ischemic stroke (OR = 0.53, 95 % CI = 0.34–0.83). Moreover, haplotype G-5G-T was associated with an increased risk of overall stroke (OR = 1.28, 95 % CI = 1.01–1.62). In contrast, haplotype A-4G-G and haplotype G-5G-T were slightly associated with the protection from ischemic stroke (OR = 0.61, 95 % CI = 0.46–0.82; OR = 0.61, 95 % CI = 0.44–0.85, respectively). The study assessed the associations of three PAI-1 SNPs and also suggested combined effects of these PAI-1 gene variants and COC use on stroke risk in the Han Chinese women.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (No. 30972542), National 11th Five Year-Plan Key Projects (2006BAI15B07) and Jiangsu Province Science and Technology Agency Program (BM2012062). Our sincere thanks go to Zhiming Sun, Jian Zhou, Lei Ba, Yulin Wu, Xiangjun Zhu, and Ying Chen (NPFPC Contraceptives Adverse Reaction Monitoring Center, Jiangsu Institute of Planned Parenthood Research, China) for their help in study working and data collecting.

Conflict of Interest

All authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Epidemiology & Biostatistics, School of Public Health, Nanjing Medical University, 818 East Tianyuan Road, Jiangning District, Nanjing, 211166, Jiangsu, China

    Xiaoping Huang, Ying Li & Zhenlin Xu

  2. Jiangsu Institute of Planned Parenthood Research, 277 Feng Huang Xi Jie, Nanjing, 210036, Jiangsu, China

    Ying Li

  3. Suzhou Center for Disease Prevention and Control, 72 Sanxiang Road, Suzhou, 215000, China

    Zhizheng Huang

  4. Department of Occupational Medicine and Environmental Toxicology, Nantong University, 9 Se Yuan Road, Nantong, 226000, China

    Chun Wang

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  1. Xiaoping Huang
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Correspondence to Ying Li.

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Huang, X., Li, Y., Huang, Z. et al. Pai-1 Gene Variants and COC Use Are Associated with Stroke Risk: A Case-Control Study in the Han Chinese Women. J Mol Neurosci 54, 803–810 (2014). https://doi.org/10.1007/s12031-014-0418-0

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