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A beneficial effect of simvastatin on DNA damage in 242T allele of the NADPH oxidase p22phox in hypercholesterolemic patients

Authors
 Min-Jeong Shin  ;  Eun Young Cho  ;  Namsik Chung  ;  Hyun Young Park  ;  Sung-Soon Kim  ;  Young-Guk Ko  ;  Jong-Won Ha  ;  Seok-Min Kang  ;  Se-Joong Rim  ;  Seung-Yun Cho  ;  Won-Heum Shim  ;  Jong Ho Lee  ;  Yangsoo Jang 
Citation
 CLINICA CHIMICA ACTA, Vol.360(1-2) : 46-51, 2005 
Journal Title
CLINICA CHIMICA ACTA
ISSN
 0009-8981 
Issue Date
2005
MeSH
Aged ; Alleles ; Anticholesteremic Agents/administration & dosage ; Anticholesteremic Agents/pharmacology ; Comet Assay ; DNA Damage/drug effects* ; Female ; Gene Frequency ; Genotype ; Humans ; Hypercholesterolemia/drug therapy* ; Hypercholesterolemia/genetics* ; Lymphocytes ; Male ; Membrane Transport Proteins/genetics* ; Middle Aged ; NADPH Oxidases/genetics* ; Oxidation-Reduction ; Phosphoproteins/genetics* ; Polymorphism, Single Nucleotide ; Simvastatin/administration & dosage ; Simvastatin/pharmacology*
Keywords
NADPH oxidase ; Polymorphism ; DNA damage ; Simvastatin
Abstract
BACKGROUND: The effect of simvastatin on DNA damage in hypercholesterolemic patients was investigated, and the relationship between the C242T polymorphism of the NADPH oxidase p22phox gene and the antioxidant effects of simvastatin was examined.
METHODS: Simvastatin (20-40 mg /day) was administered for 8 weeks in 72 hypercholesterolemic patients. DNA damage in lymphocytes was quantified using single-cell gel electrophoresis (COMET assay) by measuring tail DNA (%), tail length (microm) and tail moment (tail length x % tail DNA/100).
RESULTS: Simvastatin significantly reduced DNA damage as expressed by tail DNA (%, p< 0.001), tail length (mum, p<0.001) and tail moment on the DNA in lymphocytes (p<0.001) after 8 weeks. The frequencies of the C242T genotypes for CC, TC, and TT were 75.0%, 23.6% and 1.4% in the subjects. In the presence of the 242T allele, there were higher levels of baseline DNA damage and also a greater improvement in the DNA damage after 8 week simvastatin treatment compared with the CC homozygotes.
CONCLUSION: Simvastatin significantly reduced DNA damage of hypercholesterolemic patients. This study showed that simvastatin has a beneficial effect on the improvement of DNA damage in patients with the 242T allele of NADPH oxidase p22phox gene.
Full Text
http://www.sciencedirect.com/science/article/pii/S0009898105002457
DOI
10.1016/j.cccn.2005.04.001
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Min(강석민) ORCID logo https://orcid.org/0000-0001-9856-9227
Ko, Young Guk(고영국) ORCID logo https://orcid.org/0000-0001-7748-5788
Kim, Sung Soon(김성순)
Shim, Won Heum(심원흠)
Rim, Se Joong(임세중) ORCID logo https://orcid.org/0000-0002-7631-5581
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Chung, Nam Sik(정남식)
Cho, Seung Yun(조승연)
Ha, Jong Won(하종원) ORCID logo https://orcid.org/0000-0002-8260-2958
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114796
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