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Polymorphisms of steroid 5- α- reductase type I (SRD5A1) gene are associated to peripheral arterial disease

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Abstract

Although animal studies support the hypothesis that androgenic biological actions may affect experimental atherosclerosis progression, evidence for a relationship between androgen effects and peripheral arterial disease (PAD), a common clinical form of atherosclerosis, is weak or contradictory. Testosterone, the main androgen hormone, is converted in a 5α-reduced form by enzymatic activities in the target cells and some specific actions are mediated by such metabolites. Steroid 5-α reductase isoenzymes (SRD5A1 and SRD5A2) catalyze the conversion to the bioactive potent androgen dihydrotestosterone and other reduced metabolites and represent relevant regulators of local hormonal actions. In the present study we tested for the association of selected single nucleotide polymorphisms (SNP) of SRD5A1 and SRD5A2 with symptomatic PAD patients. Two different SNP in the SRD5A1 were significantly associated which the PAD phenotype (p<0.03, odds ratio 1.73), while no association was found between PAD phenotypes and SRD5A2. Since the examined SRDA1 gene variant was previously associated with a low enzymatic activity, we suggest that a decreased local enzymatic conversion of testosterone may contribute to PAD genetic susceptibility.

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Authors and Affiliations

  1. Department of Internal Medicine and Systemic Diseases, Medical Angiology Section, c/o Ospedale Garibaldi, Piazza S. Maria di Gesù 7, 95123, Catania, Italy

    S. S. Signorelli MD, M. Anzaldi & V. Fiore

  2. Department of Chemical Sciences, Section of Biochemistry and Molecular Biology, Faculty of Medicine, University of Catania, Catania

    V. Barresi, N. Musso & D. F. Condorelli

  3. Vascular Surgery Unit, “R. Guzzardi” Hospital, Vittoria, Italy

    E. Croce

Authors
  1. S. S. Signorelli MD
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  2. V. Barresi
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  3. N. Musso
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  4. M. Anzaldi
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  5. E. Croce
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  6. V. Fiore
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  7. D. F. Condorelli
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Correspondence to S. S. Signorelli MD.

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Signorelli, S.S., Barresi, V., Musso, N. et al. Polymorphisms of steroid 5- α- reductase type I (SRD5A1) gene are associated to peripheral arterial disease. J Endocrinol Invest 31, 1092–1097 (2008). https://doi.org/10.1007/BF03345658

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