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| The beneficial effect of simvastatin on oxidative DNA damage in 242T allele of the NADPH oxidase p22phox in hypercholesterolemic patients |
| Yonsei Cardiovascular Center, Yonsei University¹ |
| Min-Jeong Shin¹, Namsik Chung¹, Eun Young Cho¹, Yangsoo Jang¹, Jong Ho Lee¹, Hyun Young Park¹ , Won-Heum Shim¹, Seung-Yun Cho¹, Se-Joong Rim¹, Seok-Min Kang¹, Jong-Won Ha¹, Young-Guk Ko¹, Sung-Soon Kim¹ |
We investigated the effects of simvastatin on oxidative DNA damage in lymphocytes of hypercholesterolemic patients, and the relationship between C242T polymorphism of NADPH oxidase p22phox gene and the antioxidant effects of simvastatin. 20-40 mg /day of simvastatin was administered for 8 weeks in seventy-two hypercholesterolemic patients (mean age 59 years, 21 males and 51 females). Single cell gel electrophoresis (SCGE, COMET assay) was used for quantification of oxidative DNA damage in lymphocytes as measured by tail DNA (%), tail length (µm) and tail moment (tail length * % tail DNA / 100) before and 8 weeks after adminstration. Simvastatin treatment showed a significant improvement in DNA damage. The quantity of tail DNA and tail length were significantly decreased from 10.5± 2.3 to 8.8 ± 2.2 % (p<0.001) and from 55.5 ± 14.2 to 44.5 ± 15.3 µm (p<0.001), respectively. In addition, tail moment was significantly decreased from 7.5 ± 2.5 to 5.2 ± 2.5 (p<0.001). Significant correlations were noted between the degree of baseline DNA damage and the degree of improvement after simvastatin (tail DNA: r= 0.586, p<0.001; tail length: r=0.580, p<0.001; tail moment: r=0.579, p<0.001). The frequencies of the C242T genotypes for CC, TC, and TT were 75.0%, 23.6% and 1.4% in the subjects. T allele frequency was 0.13. There were no differences in age, sex, blood lipid profile between the CC homozygotes and T allele (TC+TT). At baseline, the levels of tail DNA (%) and tail length (µm) were significantly higher in the subjects with the TC+TT genotypes compared with in the subjects with the CC homozygotes (tail DNA : p<0.05, tail length : p <0.05). In the presence of 242T allele, there were a significant greater improvement in the DNA damage after 8 week simvastatin treatment compared with the CC homozygotes (tail DNA : -1.3 ± 2.3 vs –3.1 ± 3.1, p=0.02; tail length : -8.1± 17.6 vs –19.8 ± 19.1, p=0.035; tail moment : -1.7 ± 2.9 vs –4.1 ± 2.5, p=0.005). This pharmacogenetic study demonstrated the beneficial effect of simvastatin on the improvement oxidative DNA damage in those with 242T allele of NADPH oxidase.
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