HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: db08-0450v1 57/10/2794    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Asleh, R. Articles by Levy, A. P. PubMed PubMed Citation Articles by Asleh, R. Articles by Levy, A. P. Social Bookmarking                What's this?

Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype

¹ Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
² Lipid Research Laboratory, Rambam Medical Center, Haifa, Israel
³ Clinical Research Unit, Clalit Health Services, Haifa and Western Galilee, Israel
⁴ Department of Family Medicine, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
⁵ Clalit Health Services, Haifa and Western Galilee, Israel
⁶ Lady Davis Carmel Medical Center, Haifa, Israel
⁷ Department of Physiology and Biophysics, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

Corresponding author: Andrew P. Levy, alevy{at}tx.technion.ac.il

OBJECTIVE—Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of diabetic individuals). However, because of the large number of clinical trials that failed to demonstrate benefit from vitamin E coupled with the lack of a mechanistic explanation for why vitamin E should be beneficial only in diabetic individuals with the Hp 2-2 genotype, enthusiasm for this pharmacogenomic paradigm has been limited. In this study, we sought to provide such a mechanistic explanation based on the hypothesis that the Hp 2-2 genotype and diabetes interact to promote HDL oxidative modification and dysfunction.

RESEARCH DESIGN AND METHODS—Hb and lipid peroxides were assessed in HDL isolated from diabetic individuals or mice with the Hp 1-1 or Hp 2-2 genotypes. HDL function was assessed based on its ability to promote cholesterol efflux from macrophages. A crossover placebo-controlled study in Hp 2-2 diabetic humans and in Hp 1-1 and Hp 2-2 diabetic mice assessed the ability of vitamin E to favorably modify these structural and functional parameters.

RESULTS—Hb and lipid peroxides associated with HDL were increased and HDL function was impaired in Hp 2-2 diabetic individuals and mice. Vitamin E decreased oxidative modification of HDL and improved HDL function in Hp 2-2 diabetes but had no effect in Hp 1-1 diabetes.

CONCLUSIONS—Vitamin E significantly improves the quality of HDL in Hp 2-2 diabetic individuals.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?