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


CONCLUSIONS
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.
Shin
Min-Jeong
MJ
Yonsei Cardiovascular Research Institute, Yonsei University College of Medicine, Seodaemun-gu, Seoul 120-752, Republic of Korea.
Cho
Eun Young
EY
Jang
Yangsoo
Y
Lee
Jong Ho
JH
Shim
Won-Heum
WH
Cho
Seung-Yun
SY
Rim
Se-Joong
SJ
Kang
Seok-Min
SM
Ha
Jong-Won
JW
Ko
Young-Guk
YG
Kim
Sung-Soon
SS
Park
Hyun Young
HY
Chung
Namsik
N
D000368:Aged; D000483:Alleles; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics*; D008214:Lymphocytes; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D010084:Oxidation-Reduction; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D019821:Simvastatin; D019255:NADPH Oxidases; C086986:CYBA protein, human