title: The effects of rosuvastatin on lipid-lowering, inflammatory, antioxidant and fibrinolytics blood biomarkers are influenced by Val16Ala superoxide dismutase manganese-dependent gene polymorphism.
abstract: Rosuvastatin is a cholesterol-lowering drug that also attenuates the inflammatory process and oxidative stress via the reduction of superoxide anion production. Superoxide anions are metabolized by manganese-dependent superoxide dismutase (MnSOD or SOD2) in the mitochondria. In humans, there is a gene polymorphism where a change of alanine (Ala) to valine (Val) occurs at the 16th amino acid (Ala16Val-SOD2). The VV genotype has been associated with the risk of developing several metabolic diseases, such as hypercholesterolemia. Thus, to further explore this phenomenon, this study investigated the influence of the Val16Ala-SOD2 polymorphism on the lipid profile and inflammatory and fibrinolytic biomarkers of 122 hypercholesterolemic patients undergoing the first pharmacological cholesterol-lowering therapy who were treated with 20 mg rosuvastatin for 120 days. The findings indicate that the VV patients who present a low-efficiency SOD2 enzyme exhibit an attenuated response to rosuvastatin compared with the A-allele patients. The effect of rosuvastatin on inflammatory and fibrinolytic biomarkers was also less intense in the VV patients. These results suggest some pharmacogenetic effects of Val16Ala-SOD2 in hypercholesterolemia treatment.
authors.affiliation: Postgraduate Program in Pharmacology, Biogenômica Laboratory, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: T
authors.initials: T
authors.lastname: Duarte
authors.affiliation: Department of Morphology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: I B M
authors.initials: IB
authors.lastname: da Cruz
authors.affiliation: Postgraduate Program in Pharmacology, Biogenômica Laboratory, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Barbisan
authors.affiliation: Postgraduate Program in Pharmacology, Biogenômica Laboratory, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: D
authors.initials: D
authors.lastname: Capelleto
authors.affiliation: Department of Clinical and Toxicological Analysis, Center of Health Sciences, Labiclin Laboratory, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: R N
authors.initials: RN
authors.lastname: Moresco
authors.affiliation: Postgraduate Program in Pharmacology, Biogenômica Laboratory, Federal University of Santa Maria, Santa Maria, Brazil.|Center of Health Sciences, Lutheran University of Brazil, Canoas, Brazil.
authors.forename: M M M F
authors.initials: MM
authors.lastname: Duarte
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D018836:Inflammation Mediators / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000235:genetics*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000099156:Superoxide Dismutase 2
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D002784:Cholesterol; D005343:Fibrinolytic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D000068718:Rosuvastatin Calcium; D013482:Superoxide Dismutase; D013481:Superoxides; D000099156:Superoxide Dismutase 2