Abstract
Background: Erythropoietin has a pivotal role in erythropoiesis and angiogenesis. A common polymorphism (rs1617640, A > C) in the promoter of the erythropoietin gene (EPO) has been associated with erythropoietin expression and microvascular complications of diabetes. We aimed to analyze the potential role of this polymorphism in the pathogenesis of peripheral arterial disease (PAD). Methods: EPO genotypes and laboratory markers for erythropoiesis were determined in 945 patients with PAD. Results: The minor EPO rs1617640 C-allele was associated in an allele-dose-dependent manner with hemoglobin levels (p = 0.006), hematocrit (p = 0.029), and red blood cell count (p = 0.003). In a multivariate linear regression analysis including conventional risk factors diabetes, sex, and smoking, EPO genotypes were furthermore associated with age at onset of PAD symptoms (p = 0.009). Conclusions: The EPO rs1617640 gene polymorphism affects erythropoiesis, leads to an earlier onset of PAD, and is a potential biomarker for the pathogenesis of this disease.
Highlights
Peripheral arterial disease (PAD) is a chronic progressive disease resulting from reduced blood flow to tissues of the legs, usually caused by atherosclerosis of leg arteries [1,2]
erythropoietin gene (EPO) genotypes were not associated with classical peripheral arterial disease (PAD) risk factors diabetes, hypertension, hypercholesterolemia, smoking history, or male sex
We report that a functional genetic variation in the EPO promoter is associated with higher hemoglobin levels, hematocrit, and red blood cell count
Summary
Peripheral arterial disease (PAD) is a chronic progressive disease resulting from reduced blood flow to tissues of the legs, usually caused by atherosclerosis of leg arteries [1,2]. Angiogenesis, the growth of new capillaries from the existing vascular structures, is triggered by endothelial cell proliferation and migration. This process may lead to the formation of a collateral circulation functioning as “endogenous bypass vessels”. We aimed to analyze the potential role of this polymorphism in the pathogenesis of peripheral arterial disease (PAD). In a multivariate linear regression analysis including conventional risk factors diabetes, sex, and smoking, EPO genotypes were associated with age at onset of PAD symptoms (p = 0.009). Conclusions: The EPO rs1617640 gene polymorphism affects erythropoiesis, leads to an earlier onset of PAD, and is a potential biomarker for the pathogenesis of this disease
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