Superoxide Dismutase Gene Polymorphism is Associated With Ischemic Stroke Risk in the China Dali Region Han Population

Abstract

Background: Stroke is a serious cardiovascular disease, a major cause of disability and death in both developed and developing countries. Superoxide dismutases (SODs) are enzymes that catalyze the breakdown of superoxide into oxygen and hydrogen peroxide and play a key role in the antioxidant response. This study explored the relationship between single-nucleotide polymorphisms (SNPs) in SOD genes and the risk of ischemic stroke (IS) in the Chinese Han population of Dali City. Methods: For this case-control study, the authors enrolled 144 patients who had an IS and 128 healthy controls. The SNPs rs17880487 and rs80265967 of the SOD1 gene, rs4880 and rs2842960 of the SOD2 gene, and rs2695232 and rs7655372 of the SOD3 gene were detected through TaqMan polymerase chain reaction. Genotypes and allele frequencies of the 2 groups were compared. Odds ratio and 95% confidence intervals were calculated by unconditional logistic regression, and environmental factors were corrected with multivariate logistic regression analysis. Results: Rs7655372 of SOD3 was associated with a significantly increased risk of IS. Moreover, the A and GA genotypes of SNP rs7655372 were associated with increased risk of IS, whereas the A and GA genotypes were risk factors for IS. Furthermore, multivariate logistic regression analysis showed that the rs7655372 GA genotype is the independent risk factor for IS. Conclusion: The SOD3 gene rs7655372 locus polymorphism is a risk factor for IS in the Dali region.

The epigenomic landscape of single vascular cells reflects developmental origin and identifies disease risk loci

“…This observation was noted for Igfbp4 and Sod3 which have higher expression within fibroblasts isolated from the carotid artery, both of which have been implicated in risk of stroke. 54, 55 A particularly notable finding consistent with differential gene expression matching vascular bed specific disease risk is that Cyp1b1 has higher expression within the descending aorta endothelial cell population (Figure 3K). Cyp1b1 has a particularly important role in mediating the formation of abdominal aortic aneurysm in mice.…”

“…Evaluation of genes which differentiate fibroblasts from the carotid vascular bed identifies several genes with associations with stroke including Igfbp4 (insulin like growth factor binding protein 4) (Figure 3G&I, Supplemental Table 7), which has previously been found to be a plasma biomarker for ischemic stroke, 54 and Sod3 (superoxide dismutase 3) (Figure 3G&J), for which polymorphisms have been implicated in the risk for ischemic stroke. 55 Top genes which differentiate fibroblasts in the descending aorta identify genes involved in TGF signaling such as Tgfbi (Figure 3G&K, Supplemental Table 8), cell adhesion molecules such as Fbln7 (Figure 3G&L), and factors which regulate angiogenesis such as Vegfd and Serpinf1 (Figure 3G).…”

Antioxidant enzymes and vascular diseases

“…Thus, the antioxidant defense has an essential role in the homeostatic functioning of the vascular endothelial system, whereby antioxidant enzymes represent the primary line of antioxidant protection [4,59]. Numerous studies have proven the association between reduced expression and activity of antioxidant enzymes and ČVD development [68,73,80]. Hence, additional research on how ROS is utilized in the cardiovascular system and consequently impacts the regulation of antioxidant enzymes is needed to develop new diagnostic biomarkers and therapeutic strategies.…”

“…In male and female patients with idiopathic pulmonary arterial hypertension, the expressions of all three SOD isoforms were reduced compared to the healthy patients [67]. Nevertheless, gene rs7655372 locus polymorphism of SOD3 in male and female patients is a risk factor for ischemic stroke [68]. The association between SODs activities and vascular diseases is imperative for developing a new diagnostic biomarker and therapy strategy.…”

An Emerging Role of Defective Copper Metabolism in Heart Disease

“…A SOD3 R231G variant, which processes less antioxidant ability, was reported to be positively associated with IHD, myocardial infarction, and HF in diabetic subjects [ 50 , 51 , 52 , 53 , 54 ]. The rs7655372 variant of the SOD3 gene was associated with a significantly increased risk of ischemic stroke in the Chinese Han population of Dali City [ 67 ]. By contrast, a protective T-allele of the rs2284659 variant in the promoter region of the SOD3 gene was negatively associated with the incidence of myocardial infarction and cardiovascular and all-cause mortality in both type 1 and type 2 diabetic patients [ 52 ].…”