Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cardiovascular Toxicology
Published in: Cardiovascular Toxicology 2/2023

17-02-2023 | Stroke

Influence of ZFHX3 Polymorphisms on the Risk of Ischemic Stroke in Chinese Han Population

Authors: Wei Hu, Gang Wang, Pei Wang, Haitao Jin, Jianmin Liu, Xingbo Dang

Published in: Cardiovascular Toxicology | Issue 2/2023

Login to get access

Abstract

The association of ZFHX3 gene polymorphisms with ischemia stroke (IS) susceptibility has been clarified in Europeans, but not in the Chinese Han population. To assess the effect of ZFHX3 polymorphisms on IS risk, rs7193343, rs879324, and rs12932445 were selected and genotyped using the Agena MassARRAY platform in 694 patients and 687 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model adjusted for age, sex, smoking, and drinking status. The potentially influential factors for IS risk were analyzed using multifactor dimension reduction (MDR) software v3.0.2 and least absolute shrinkage and selection operator (LASSO) logistic regression. Our results displayed that rs879324 (p = 0.011, OR = 0.81) and rs12932445 (p = 0.012, OR = 0.81) were protective factors for IS in the Chinese Han population. Specifically, rs879324 had a lower susceptibility to IS in subjects aged ≤ 64 years, non-smokers, and non-drinkers (p < 0.05). Furthermore, rs12932445 was associated with a reduced risk of IS in people aged > 64 years, females, non-smokers, and non-drinkers (p < 0.05). MDR and LASSO analyses revealed that rs879324 was the most influential factor for IS risk. These findings suggested that ZFHX3 variants may be biomarkers in IS occurrence in the Chinese Han population, which may provide a new insight into the etiology of IS.
Appendix
Available only for authorised users
Literature
1.
2.
Wang, W., Jiang, B., Sun, H., Ru, X., Sun, D., Wang, L., Wang, L., Jiang, Y., Li, Y., Wang, Y., et al. (2017). Prevalence, incidence, and mortality of stroke in China: Results from a nationwide population-based survey of 480 687 Adults. Circulation, 135(8), 759–771.CrossRefPubMed
3.
Gorelick, P. B. (2019). The global burden of stroke: Persistent and disabling. The Lancet Neurology, 18(5), 417–418.CrossRefPubMed
4.
Krishnamurthi, R. V., Feigin, V. L., Forouzanfar, M. H., Mensah, G. A., Connor, M., Bennett, D. A., Moran, A. E., Sacco, R. L., Anderson, L. M., Truelsen, T., et al. (2013). Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: Findings from the Global Burden of Disease Study 2010. The Lancet Global Health, 1(5), e259-281.CrossRefPubMedPubMedCentral
5.
6.
Huang, J., Wei, Q., Liang, B., Shen, T., Wu, Y., Chen, Z., Yang, J., & Gu, L. (2021). Association of CHUK gene polymorphism and ischemic stroke in the Han Chinese population. Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia, 88, 271–276.CrossRefPubMed
7.
Kumar, A., Chauhan, G., Sharma, S., Dabla, S., Sylaja, P. N., Chaudhary, N., Gupta, S., Agrawal, C. S., Anand, K. S., Srivastava, A. K., et al. (2021). Association of SUMOylation pathway genes with stroke in a genome-wide association study in India. Neurology, 97(4), e345–e356.CrossRefPubMedPubMedCentral
8.
Dong, X., Wang, J., Wang, G., Wang, J., Wang, L., & Du, Y. (2021). MTHFR A1298C gene polymorphism on stroke risk: An updated meta-analysis. Genes and Environment: The Official Journal of the Japanese Environmental Mutagen Society, 43(1), 40.CrossRefPubMed
9.
Sun, X., Fu, X., Li, J., Xing, C., Martin, D. W., Zhang, H. H., Chen, Z., & Dong, J. T. (2012). Heterozygous deletion of Atbf1 by the Cre-loxP system in mice causes preweaning mortality. Genesis (New York, NY: 2000), 50(11), 819–827.CrossRef
10.
Jung, C. G., Kim, H. J., Kawaguchi, M., Khanna, K. K., Hida, H., Asai, K., Nishino, H., & Miura, Y. (2005). Homeotic factor ATBF1 induces the cell cycle arrest associated with neuronal differentiation. Development (Cambridge, England), 132(23), 5137–5145.CrossRefPubMed
11.
Feng, E., & Jiang, L. (2020). Peptidomic analysis of hippocampal tissue for explore leptin neuroprotective effect on the preterm ischemia–hypoxia brain damage model rats. Neuropharmacology, 162, 107803.CrossRefPubMed
12.
Kim, T. S., Kawaguchi, M., Suzuki, M., Jung, C. G., Asai, K., Shibamoto, Y., Lavin, M. F., Khanna, K. K., & Miura, Y. (2010). The ZFHX3 (ATBF1) transcription factor induces PDGFRB, which activates ATM in the cytoplasm to protect cerebellar neurons from oxidative stress. Disease Models and Mechanisms, 3(11–12), 752–762.CrossRefPubMed
13.
Yang, S. A. (2017). Association study between ZFHX3 gene polymorphisms and obesity in Korean population. Journal of Exercise Rehabilitation, 13(4), 491–494.CrossRefPubMedPubMedCentral
14.
Wu, L., Chu, M., & Zhuang, W. (2021). Association between ZFHX3 and PRRX1 polymorphisms and atrial fibrillation susceptibility from meta-analysis. International Journal of Hypertension, 2021, 9423576.CrossRefPubMedPubMedCentral
15.
Sun, S., Zhang, W., Chen, X., & Song, H. (2015). The CAA repeat polymorphism in the ZFHX3 gene is associated with risk of coronary heart disease in a Chinese population. The Tohoku Journal of Experimental Medicine, 235(4), 261–266.CrossRefPubMed
16.
Gudbjartsson, D. F., Holm, H., Gretarsdottir, S., Thorleifsson, G., Walters, G. B., Thorgeirsson, G., Gulcher, J., Mathiesen, E. B., Njølstad, I., Nyrnes, A., et al. (2009). A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nature Genetics, 41(8), 876–878.CrossRefPubMedPubMedCentral
17.
Liu, L., Ebana, Y., Nitta, J. I., Takahashi, Y., Miyazaki, S., Tanaka, T., et al. (2017). Genetic variants associated with susceptibility to atrial fibrillation in a Japanese population. The Canadian Journal of Cardiology, 33(4), 443–449.CrossRefPubMed
18.
da Silva, C. F., Schwartz, J., Belli, V. D. S., Ferreira, L. E., Cabral, N. L., & França, P. H. C. (2020). Ischemic stroke and genetic variants: In search of association with severity and recurrence in a Brazilian population. Journal of Stroke and Cerebrovascular Diseases: The Official Journal of National Stroke Association, 29(2), 104487.CrossRefPubMed
19.
Wei, Y., Wang, L., Lin, C., Xie, Y., Bao, Y., Luo, Q., & Zhang, N. (2021). Association between the rs2106261 polymorphism in the zinc finger homeobox 3 gene and risk of atrial fibrillation: Evidence from a PRISMA-compliant meta-analysis. Medicine, 100(49), e27749.CrossRefPubMedPubMedCentral
20.
McEligot, A. J., Poynor, V., Sharma, R., & Panangadan, A. (2020). Logistic LASSO regression for dietary intakes and breast cancer. Nutrients, 12(9), 2652.CrossRefPubMedPubMedCentral
21.
Parsons, M. J., Brancaccio, M., Sethi, S., Maywood, E. S., Satija, R., Edwards, J. K., Jagannath, A., Couch, Y., Finelli, M. J., Smyllie, N. J., et al. (2015). The regulatory factor ZFHX3 modifies Circadian function in SCN via an AT motif-driven axis. Cell, 162(3), 607–621.CrossRefPubMedPubMedCentral
22.
Nojiri, S., Joh, T., Miura, Y., Sakata, N., Nomura, T., Nakao, H., Sobue, S., Ohara, H., Asai, K., & Ito, M. (2004). ATBF1 enhances the suppression of STAT3 signaling by interaction with PIAS3. Biochemical and Biophysical Research Communications, 314(1), 97–103.CrossRefPubMed
23.
Chen, S., Dong, Z., Cheng, M., Zhao, Y., Wang, M., Sai, N., Wang, X., Liu, H., Huang, G., & Zhang, X. (2017). Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke. Journal of Neuroinflammation, 14(1), 187.CrossRefPubMedPubMedCentral
24.
Liu, L., Ebana, Y., Nitta, J. I., Takahashi, Y., Miyazaki, S., Tanaka, T., Komura, M., Isobe, M., & Furukawa, T. (2017). Genetic variants associated with susceptibility to atrial fibrillation in a Japanese population. The Canadian Journal of Cardiology, 33(4), 443–449.CrossRefPubMed
25.
Greenwood, T. A., & Kelsoe, J. R. (2003). Promoter and intronic variants affect the transcriptional regulation of the human dopamine transporter gene. Genomics, 82(5), 511–520.CrossRefPubMed
26.
Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., Das, S. R., de Ferranti, S., Després, J. P., Fullerton, H. J., et al. (2016). Heart disease and stroke statistics-2016 update: A Report from the American Heart Association. Circulation, 133(4), e38-360.PubMed
27.
Gu, L., Huang, J., Liang, B., Chen, Q., Xie, J., Yang, J., Yan, Y., & Tang, Q. (2018). TLR4 polymorphisms affect stroke risk and inflammatory response in Chinese ischemic stroke patients. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 39(1), 127–133.CrossRefPubMed
28.
Gu, L., Huang, J., Li, J., Huang, S., Li, M., Gong, L., Li, T., & Su, L. (2018). Association of CALM1 rs3179089 polymorphism with ischemic stroke in Chinese Han population. Neuromolecular Medicine, 20(2), 271–279.CrossRefPubMed
29.
Paul, S., & Candelario-Jalil, E. (2021). Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies. Experimental Neurology, 335, 113518.CrossRefPubMed
30.
31.
Markidan, J., Cole, J. W., Cronin, C. A., Merino, J. G., Phipps, M. S., Wozniak, M. A., & Kittner, S. J. (2018). Smoking and risk of ischemic stroke in young men. Stroke, 49(5), 1276–1278.CrossRefPubMedPubMedCentral
32.
Yang, W., Kang, D. W., Ha, S. Y., & Lee, S. H. (2021). Drinking patterns and risk of ischemic stroke in middle-aged adults: Do beneficial drinking habits indeed exist? Stroke, 52(1), 164–171.CrossRefPubMed
33.
Duan, J., Soussen, C., Brie, D., Idier, J., Wan, M., & Wang, Y. P. (2016). Generalized LASSO with under-determined regularization matrices. Signal Processing, 127, 239–246.CrossRefPubMedPubMedCentral
34.
Kayran, Y., Yayla, V., Çabalar, M., Bajrami, A., Karamanli, Y., Gedikbaşi, A., & Tanriverdİ, Z. (2019). LDL subclasses in ischemic stroke: A risk factor? Noro Psikiyatri Arsivi, 56(1), 13–17.PubMed
35.
Hindy, G., Engström, G., Larsson, S. C., Traylor, M., Markus, H. S., Melander, O., & Orho-Melander, M. (2018). Role of blood lipids in the development of ischemic stroke and its subtypes: A Mendelian randomization study. Stroke, 49(4), 820–827.CrossRefPubMedPubMedCentral
36.
You, S., Ou, Z., Zhang, W., Zheng, D., Zhong, C., Dong, X., Qiu, C., Lu, T., Cao, Y., & Liu, C. F. (2019). Combined utility of white blood cell count and blood glucose for predicting in-hospital outcomes in acute ischemic stroke. Journal of Neuroinflammation, 16(1), 37.CrossRefPubMedPubMedCentral
Metadata
Title
Influence of ZFHX3 Polymorphisms on the Risk of Ischemic Stroke in Chinese Han Population
Authors
Wei Hu
Gang Wang
Pei Wang
Haitao Jin
Jianmin Liu
Xingbo Dang
Publication date
17-02-2023
Publisher
Springer US
Keyword
Stroke
Published in
Cardiovascular Toxicology / Issue 2/2023
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-023-09783-9

Other articles of this Issue 2/2023

Cardiovascular Toxicology 2/2023 Go to the issue

OriginalPaper

Protective Effect of Sevoflurane Preconditioning on Cardiomyocytes Against Hypoxia/Reoxygenation Injury by Modulating Iron Homeostasis and Ferroptosis

OriginalPaper

Fullerene C60 Attenuates Heart Tissue Inflammation by Modulating COX-2 and TNF-Alpha Signaling Pathways in DMBA Induced Breast Cancer in Rats

Retraction Note

Retraction Note: Indoleamine 2,3-Dioxygenase 1 (IDO1) Promotes Cardiac Hypertrophy via a PI3K-AKT-mTOR-Dependent Mechanism

OriginalPaper

Metformin and Dapagliflozin Attenuate Doxorubicin-Induced Acute Cardiotoxicity in Wistar Rats: An Electrocardiographic, Biochemical, and Histopathological Approach