Polymorphic Variants of Extracellular Superoxide Dismutase Gene in a Romanian Population with Atheroma

Abstract

Extracellular superoxide dismutase (EC-SOD) is the main SOD isoform in the arterial wall contributing to cardiovascular defense against oxidative stress by removing the superoxide anion. In our study, the Thr40Ala and Arg213Gly polymorphic variants of the EC-SOD gene (SOD ( 3 )) were investigated for associations with atherosclerosis and other related factors in 144 subjects with significant atheroma (having one, two, or three major coronary arteries with >50% obstruction, and/or peripheral artery lesions, and/or carotid artery stenosis demonstrated by angiography and echography) and in 150 subjects with no significant atheroma. For the Arg213Gly polymorphism, only five heterozygous subjects were found. Although the difference in the genotype distribution for the Thr40Ala polymorphism was not statistically significant between patients with atheroma (AA 49.3%, AG 34.7%, GG 16.0%) and those without significant atheroma (AA 41.3%, AG 43.3%, GG 15.3%), there was an association of the Thr40 allele with diabetes (P = 0.03) and hypertension (P = 0.04).

Effects of Graptopetalum paraguayense consumption on serum lipid profiles and antioxidative status in hypercholesteremic subjects

“…An in vivo study reported that total serum cholesterol and obesity were associated with high common phenotype extracellular superoxide dismutase 44. Polymorphic variants of extracellular SOD gene are also reported to be associated with many diseases, such as hypertension,45 diabetes46 and certain cancers 47. Since inter‐individualized variation in antioxidant capacity may occur as a result of functional polymorphisms of genes regulating antioxidant enzyme activity, antioxidative processes may be more relevant as determinants of some diseases.…”

The role of pathway-selective insulin resistance and responsiveness in diabetic dyslipoproteinemia

“…The SOD3 protein and mRNA are present in normal liver [95,96], and plasma levels are low in T2DM patients [90]. Moreover, a human polymorphism of SOD3, Ala40Thr, was reported to occur more often in T2DM patients than in nondiabetic controls and to be associated with a higher prevalence of hypertension and worse glucose handling in these patients [97,98]. Scavengers of intracellular H 2 O 2 include peroxiredoxin [61] and glutathione peroxidase [92], both of which have been shown to affect insulin signaling in vitro.…”

Antioxidant-Induced Stress

“…Indeed, it has been postulated and partially shown, that oxidative stress in hypertension is due, at least in part, to the increase of NADPHox’s activity in vascular smooth muscle cells, fibroblasts and endothelial cells [14,15]. Polymorphisms of the genes codifying SOD and GPx have been related to oxidative stress due to decreased activity of the enzymes and high incidence of coronary artery disease [16], ischemic stroke [17,18] and atherosclerosis [19]. Polymorphisms of GST have been associated with cardiovascular events produced in smokers [20].…”