Pharmacogenomic application of the haptoglobin genotype in the treatment of HDL dysfunction

Abstract

An emerging paradigm of research has suggested that in the setting of diabetes mellitus (DM) the quality or function of high-density lipoprotein (HDL) may be a determinant of cardiovascular disease risk. Specifi c structural modifi cations of HDL protein and lipid components, resulting from oxidative modifi cation, have been proposed to mediate HDL's loss of the ability to promote cholesterol effl ux (reverse cholesterol transport), serve as an antioxidant and anti-infl ammatory agent. Therefore, inhibiting HDL oxidative modifi cation would be expected to improve its function and provide cardioprotection. Nevertheless, antioxidant strategies to reduce cardiovascular events from atherosclerosis in DM have failed. It has been proposed that this failure may have been due to the inadequate nature of patient selection. High dose antioxidant therapy may only provide benefi t to a subset of DM individuals with oxidatively modifi ed HDL. We will review evidence that haptoglobin (Hp) identifi es such individuals who can be successfully treated with vitamin E. These data will suggest that a pharmacogenomic approach utilizing the Hp genotype may be useful in identifying individuals who will benefi t from antioxidant therapy. © 2009 Schwartz et al, publisher and licensee Dove Medical Press Ltd.