| First Author | Asleh R | Year | 2008 |
| Journal | Diabetes | Volume | 57 |
| Issue | 10 | Pages | 2794-800 |
| PubMed ID | 18599520 | Mgi Jnum | J:141887 |
| Mgi Id | MGI:3819993 | Doi | 10.2337/db08-0450 |
| Citation | Asleh R, et al. (2008) Correction of HDL dysfunction in individuals with diabetes and the haptoglobin 2-2 genotype. Diabetes 57(10):2794-800 |
| abstractText | 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. |
