A Functional Polymorphism in HIF-3\u03b1 Is Related to an Increased Risk of Ischemic Stroke

Xi-Xi Gu,Yong-Ling He,Wu-Xiang Shi,Ye-Sheng Wei,Zhi-Neng Zeng,Yong-Chao Qiao,Zhuan-Zhi Tang

doi:10.1007/s12031-020-01728-z

Xi-Xi Gu, Yong-Ling He + Show 5 more

Open Access

https://doi.org/10.1007/s12031-020-01728-z

Copy DOI

Abstract

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.

Highlights

Stroke is considered to be the main cause of death and permanent disability worldwide, causing serious economic and social impacts (Amp and Wilkins 2017; Brand et al 2009; Susan a. Randolph 2016)
TG, total cholesterol (TC), apolipoprotein B (Apo-B), non-esterified fatty acid (NEFA), and homocysteic acid (Hcy) levels were significantly higher in Ischemic stroke (IS) patients, while high-density lipoprotein cholesterol (HDL-C) and apolipsprotein A1 (Apo-A1) levels were lower in control groups (P all < 0.001)
The results are shown in Table 5; the risk factors contained TG (OR = 1.02; 95% confidence interval (CI) = 0.86–1.20, P = 0.85), TC (OR = 1.37; 95% CI = 1.08–1.73), HDL-C (OR = 1.00; 95% CI = 0.93– 1.08), Apo-A1 (OR = 0.00; 95% CI = 0.00–0.01), Apo-B (OR = 52.76; 95% CI = 18.90–147.21), Hcy

Summary

Introduction

Stroke is considered to be the main cause of death and permanent disability worldwide, causing serious economic and social impacts (Amp and Wilkins 2017; Brand et al 2009; Susan a. Randolph 2016). Stroke is considered to be the main cause of death and permanent disability worldwide, causing serious economic and social impacts Likewise, both the life quality and expectancy of life in patients are seriously influenced. Ischemic stroke (IS) is a more common type, and it accounts for approximately 85% of total cases (Rosamond et al 2007). Xi-Xi Gu and Zhuan-Zhi Tang contributed to this work. The occurrence and development of IS are affected by a host of risk factors, including environmental and genetic risk factors (Feigin et al 2009; Fonseca and Ferro 2015; Guzik and Bushnell 2017; Hankey 2014)

Methods

Results

Conclusion