期刊
PHARMACOGENOMICS
卷 11, 期 5, 页码 675-684出版社
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.10.17
关键词
antioxidants; cardiovascular disease; diabetes mellitus; haptoglobin; hemoglobin; pharmacogenomics; vitamin E
资金
- United States Israel Binational Science Foundation
- Israel Science Foundation
- Juvenile Diabetes Research Foundation
- Kennedy Leigh Charitable Trust
- NIH [RO1KD085226]
- US Agency for Healthcare Research and Quality [R21HS017643-01]
- Kaiser Permanente Center for Health Research
Aims: Individuals with both diabetes mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype are at increased risk of cardiovascular disease. As the antioxidant function of the Hp 2-2 protein is impaired, we sought to test the pharmacogenomic hypothesis that antioxidant vitamin E supplementation would provide cardiovascular protection to Hp 2-2 DM individuals. Materials & methods: We determined the Hp genotype on DM participants from two trials (HOPE and ICARE) and assessed the effect of vitamin E by Hp genotype on their common prespecified outcome, the composite of stroke, myocardial infarction and cardiovascular death. Data was analyzed with a fixed-effect model. These results were input into a simulation model, the Evidence Based Medicine Integrator, in order to estimate their long-term implications in a real-world population from Kaiser Permanente (CA, USA). Results: Meta-analysis of the two trials demonstrated a significant overall reduction in the composite end point in Hp 2-2 DM individuals with vitamin E (odds ratio: 0.58; 95% CI: 0.40-0.86; p = 0.006). There was a statistically significant interaction between the Hp genotype and vitamin E on the composite end point. In these trials, Hp typing of 69 DM individuals and treating those with the Hp 2-2 with vitamin E prevented one myocardial infarct, stroke or cardiovascular death. Lifelong administration of vitamin E to Hp 2-2 DM individuals in the Kaiser population would increase their life expectancy by 3 years. Conclusion: A pharmacogenomic strategy of screening DM individuals for the Hp genotype and treating those with Hp 2-2 with vitamin E appears to be highly clinically effective.
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