A Functional Polymorphism in HIF-3α Is Related to an Increased Risk of Ischemic Stroke

Hypoxia-inducible factor-3α ( HIF-3α ), a member of HIF family, can mediate adaptive responses to low oxygen and ischemia. It is believed that HIF plays crucial roles in stroke-related diseases. However, there are no reports on the association between HIF-3α genetic variants and ischemic stroke (IS)...

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Bibliographic Details
Published in:Journal of molecular neuroscience 2021-05, Vol.71 (5), p.1061-1069
Main Authors: Gu, Xi-Xi, Tang, Zhuan-Zhi, He, Yong-Ling, Zeng, Zhi-Neng, Shi, Wu-Xiang, Qiao, Yong-Chao, Wei, Ye-Sheng
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cell Biology
Confidence intervals
Esterification
Fatty acids
Gene frequency
Gene polymorphism
Genetic diversity
Genetic variance
Health risks
Hypoxia
Hypoxia-inducible factors
Ischemia
Neurochemistry
Neurology
Neurosciences
Polymorphism
Population studies
Proteomics
Regression analysis
Risk analysis
Risk factors
Statistical analysis
Stroke
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Summary:Hypoxia-inducible factor-3α ( HIF-3α ), a member of HIF family, can mediate adaptive responses to low oxygen and ischemia. It is believed that HIF plays crucial roles in stroke-related diseases. However, there are no reports on the association between HIF-3α genetic variants and ischemic stroke (IS) susceptibility. Therefore, we examined the association between HIF- 3α gene polymorphisms (rs3826795, rs2235095, and rs3764609) and IS risk. The study population included 302 controls and 310 patients with ischemic stroke. Three polymorphisms in HIF- 3α (rs3826795, rs2235095, and rs3764609) were genotyped using SNPscan technique. Our study showed a strong association of rs3826795 in HIF-3α with the risk of IS. The genotype and allele frequencies were shown to differ between the two groups. The rs3826795 in an intron of HIF-3α was related to a prominent increased IS risk (AA vs GG adjusted odd ratio [OR], 2.21; 95% confidence intervals [95% CI], 1.10–4.44; P  = 0.03; AA vs AG/GG OR = 1.74, 95% CI, 1.02–2.97, P  = 0.04; A vs G OR = 1.48, 95% CI, 1.05–2.07, P  = 0.02). Logistic regression analysis suggested that rs3826795 posed a risk factor for IS in addition to common factors. Furthermore, when compared to controls, increased levels of homocysteic acid and level of non-esterified fatty acid were found in the cases ( P  
ISSN:0895-8696
1559-1166
DOI:10.1007/s12031-020-01728-z