|M.Sc Student||Pollak Mordechai|
|Subject||Influence of Vitamin E Supplementation on HDL Structure and|
Function in DM Patients
|Department||Department of Medicine||Supervisor||Professor Andrew Peter Levy|
|Full Thesis text|
Vitamin E provides cardiovascular protection to individuals with Diabetes Mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype but appears to increase cardiovascular risk in individuals with DM and the Hp 2-1 genotype.
The goal of this work was to test the hypothesis that this pharmacogenetic interaction on cardiovascular risk might be secondary to a parallel interaction between the Hp genotype and vitamin E on HDL structure and function.
Sixty individuals with DM and the Hp 2-1 or 2-2 genotypes were studied in a double-blind placebo controlled crossover design. Participants were treated with either vitamin E (400 IU) or placebo for 3 months and crossed over for an equivalent duration. Serum was collected at baseline and after the completion of each treatment. HDL was purified by affinity chromatography using a protocol developed specifically for this study. HDL functionality as well as HDL associated markers of oxidation and inflammation were measured in all samples.
Compared to placebo, vitamin E significantly increased HDL function in Hp 2-2 DM individuals but significantly decreased HDL function in Hp 2-1 DM. This pharmacogenetic interaction was paralleled by similar differences in HDL associated lipid peroxides, glutathione peroxidase, and inflammatory cargo.
Vitamin E protects HDL structure and improves HDL function in Hp 2-2 DM patients, but causes the opposite effect in Hp 2-1 DM patients. We conclude that there is a pharmacogenetic interaction between the Hp genotype and vitamin E on HDL function and structure.