Key result
HIF-3α rs3826795 AA genotype is linked to ~121% higher ischemic stroke risk versus GG genotype.
Why the study?
There were no reports on the association between HIF-3α genetic variants and ischemic stroke susceptibility.
Are HIF-3α gene polymorphisms associated with an increased risk of ischemic stroke?
Case-Control (n=612)
No
Are HIF-3α gene polymorphisms associated with an increased risk of ischemic stroke?
Odds Ratio: 2.21 (95% CI 1.1–4.44)
Absolute Event Rate: 30.6% vs 23.5%
p-value: p=0.03
The rs3826795 polymorphism in the HIF-3α gene is associated with an increased risk of ischemic stroke, suggesting it may serve as a potential genetic marker for susceptibility.
Should not yet inform clinical stroke risk assessment; hypothesis-generating for HIF-3α variants as susceptibility markers.
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 < 0.01). However, no significant association was found between rs2235095 or rs3264609 and IS risk. These findings indicated that the rs3826795 polymorphism may be a potential target for predicting the risk of IS.
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Gu et al. (2020) conducted a case-control in Ischemic stroke (n=612). HIF-3α rs3826795 AA genotype vs. HIF-3α rs3826795 GG genotype was evaluated on Risk of ischemic stroke (OR 2.21, 95% CI 1.10-4.44, p=0.03). The HIF-3α rs3826795 AA genotype was associated with a significantly increased risk of ischemic stroke compared to the GG genotype (OR 2.21).
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