Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Blum
Shany
S
Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Vardi
Moshe
M
Brown
Jonathan B
JB
Russell
Allen
A
Milman
Uzi
U
Shapira
Chen
C
Levy
Nina S
NS
Miller-Lotan
Rachel
R
Asleh
Rabea
R
Levy
Andrew P
AP
D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism*; D020521:Stroke / Q000235:genetics / Q000378:metabolism; D024505:Tocopherols / Q000378:metabolism / Q000494:pharmacology; D014810:Vitamin E / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D000975:Antioxidants; D006242:Haptoglobins; D014810:Vitamin E; D024505:Tocopherols