Abstract
BackgroundTo determine if the rs7079 polymorphism located in the 3′ UTR of the angiotensinogen gene (AGT) altered AGT gene expression and the risk of lead poisoning. A case-control study and luciferase reporter gene assay identified a significant association between rs7079 variants and the risk of lead poisoning.ResultsSerum AGT levels were significantly higher in individuals carrying the rs7079 CA genotype, as compared to those carrying the rs7079 CC genotype. The binding of the miRNA mimics miR-31-5p and miR-584-5p to the 3′ UTR of AGT differed based on which rs7079 variant was present, implying that AGT gene expression depends on the rs7079 variant carried.ConclusionsThe rs7079 C to A substitution reduced the binding of miR-31-5p/miR-584-5p to the 3′ UTR of AGT, possibly altering the risk of lead poisoning.
Highlights
Lead is an important toxic agent that may be associated with population-level variations in cardiovascular disease rates [1]
Individuals who had smoked at least 1 cigarette per day for at least 1 year were defined as smokers, and individuals who consumed 3 or more alcoholic drinks per week for at least 1 year were considered drinkers [20]
Demographic characteristics of the study population There were no significant differences between the case and control groups with respect to age, sex, drinking status, and smoking status (P > 0.05 for all; Table 1)
Summary
Lead is an important toxic agent that may be associated with population-level variations in cardiovascular disease rates [1]. Animal studies have shown that acute and chronic lead exposure cause hypertension and cardiovascular disease by altering the renin-angiotensin-aldosterone system: increasing angiotensin-converting enzyme activity [2, 8, 9], inhibiting Na+-K+-ATPase [10], inducing oxidative stress, reducing nitric oxide bioavailability, [11, 12] and depleting antioxidant reserves [13]. Many studies have provided new insights into the mechanisms by which lead can influence vascular function. These mechanisms have been proposed to explain lead-induced hypertension, its etiology remains unclear. A case-control study and luciferase reporter gene assay identified a significant association between rs7079 variants and the risk of lead poisoning
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