Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec 9;9(1):18627.
doi: 10.1038/s41598-019-55201-y.

Association of genetic polymorphisms in CASP7 with risk of ischaemic stroke

Zhaoshi Zheng  1 , Songyan Liu  1 , Chuheng Wang  2 , Chunhui Wang  3 , Dong Tang  1 , Yuqing Shi  1 , Xuemei Han  4
Affiliations

Association of genetic polymorphisms in CASP7 with risk of ischaemic stroke

Zhaoshi Zheng et al. Sci Rep. .

Abstract

Caspase 7 (CASP7) is located on chromosome 10q25.3 that has been identified to be a susceptibility locus of ischaemic stroke (IS) by genome-wide association study. Elevated CASP7 was observed in IS, acting as a key apoptotic mediator in the development of IS. The aim of this study was to investigate the association between genetic polymorphisms in CASP7 and risk of IS. The CASP7 polymorphisms were genotyped using a TaqMan allelic discrimination assay. The expression levels of CASP7 mRNA were examined using quantitative polymerase chain reaction and luciferase activity was analyzed using the Dual Luciferase reporter assay. The rs12415607 in the promoter of CASP7 was associated with a reduced risk of IS (AA vs. CC: adjusted OR = 0.55, 95% CI: 0.38-0.80, P = 0.002; CA/AA vs. CC: adjusted OR = 0.70, 95% CI: 0.54-0.91, P = 0.007; AA vs. CC/CA: adjusted OR = 0.64, 95% CI: 0.46-0.90, P = 0.01; A vs. C: adjusted OR = 0.74, 95% CI: 0.62-0.89, P = 0.001). Moreover, the rs12415607 AA genotype carriers exhibited lower levels of CASP7 mRNA and the rs12415607 A allele decreased the promoter activity. These findings indicate that the rs12415607 A allele induces lower levels of transcriptional activity and CASP7 mRNA, and thus is associated with a reduced risk of IS.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Relative expression of CASP7 mRNA in IS patients and controls. (A) The relative expression of CASP7 mRNA in IS patients and controls (n = 86); (B) The relative expression of CASP7 mRNA in control subjects carrying the rs12415607 CC, CA, and AA genotype; (C) The relative expression of CASP7 mRNA in IS patients carrying the rs12415607 CC, CA, and AA genotype. Aligned dot plot shows median with interquartile range (*P < 0.05).
Figure 2
Figure 2
The lower levels of CASP7 mRNA in the rs12415607 AA carriers were confirmed by eQTL. (A) eQTL shows lower levels of CASP7 mRNA in multiple tissues except for testis; Representative data was presented in single tissue, such as whole blood (B), anterior cingulate cortex (C), caudate (basal ganglia) (D), nucleus accumbens (basal ganglia) (E), putamen (basal ganglia) (F), and substantia nigra (G).
Figure 3
Figure 3
The rs12415607 A allele in the promoter region of CASP7 reduced the luciferase activity. (A) Schematic representation of CASP7 promoter containing the rs12415607 C/A into pGL3 vector. TSS, transcriptional start site. (B) The CASP7 promoter containing the rs12415607 C or A was inserted into pGL3 vector and transfected into HEK293 cells. At 48 h after transfection, the promoter activity was measured using the Dual Luciferase Reproter assay. Data are presented as mean ± standard error (n = 3, **P < 0.01).
See this image and copyright information in PMC

References

    1. Bonita R, et al. The global stroke initiative. The Lancet. Neurology. 2004;3:391–393. doi: 10.1016/S1474-4422(04)00800-2. - DOI - PubMed
    1. Weinstein JR, Koerner IP, Moller T. Microglia in ischemic brain injury. Future neurology. 2010;5:227–246. doi: 10.2217/fnl.10.1. - DOI - PMC - PubMed
    1. Adams HP, Jr., et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke; a journal of cerebral circulation. 2007;38:1655–1711. doi: 10.1161/STROKEAHA.107.181486. - DOI - PubMed
    1. Feigin VL, et al. Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet. 2014;383:245–254. doi: 10.1016/S0140-6736(13)61953-4. - DOI - PMC - PubMed
    1. Yong H, et al. A systematic literature review of risk factors for stroke in China. Cardiology in review. 2013;21:77–93. doi: 10.1097/CRD.0b013e3182748d37. - DOI - PubMed

Publication types

MeSH terms