Document Detail


Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype.
MedLine Citation:
PMID:  20415560     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Shany Blum; Moshe Vardi; Jonathan B Brown; Allen Russell; Uzi Milman; Chen Shapira; Nina S Levy; Rachel Miller-Lotan; Rabea Asleh; Andrew P Levy
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Pharmacogenomics     Volume:  11     ISSN:  1744-8042     ISO Abbreviation:  Pharmacogenomics     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-26     Completed Date:  2010-07-21     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  100897350     Medline TA:  Pharmacogenomics     Country:  England    
Other Details:
Languages:  eng     Pagination:  675-84     Citation Subset:  IM    
Affiliation:
Technion Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / metabolism,  pharmacology*
Cardiovascular Diseases / genetics,  metabolism
Diabetes Mellitus / genetics,  metabolism*
Genotype
Haptoglobins / genetics*,  metabolism,  pharmacology
Humans
Myocardial Infarction / genetics,  metabolism*
Stroke / genetics,  metabolism
Tocopherols / metabolism,  pharmacology
Vitamin E / genetics,  metabolism,  pharmacology*
Grant Support
ID/Acronym/Agency:
R01 DK085226-01A1/DK/NIDDK NIH HHS; R01KD085226//PHS HHS; R21HS017643-01/HS/AHRQ HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Haptoglobins; 1406-18-4/Vitamin E; 1406-66-2/Tocopherols
Comments/Corrections

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