The effect of supplementation with an antioxidant preparation on LDL-oxidation is determined by haptoglobin polymorphism

The genetic polymorphism of haptoglobin (Hp) is an independent risk factor in the pathogenesis of atherosclerosis, a condition in which decreased resistance to in vitro oxidation of LDL-cholesterol is observed. We hypothesised that the Hp polymorphism is one of the factors modulating the resistance to Cull-induced oxidation of LDL during antioxidant supplementation. In this study, 74 middle-aged subjects with increased oxidative stress were allocated to either matched placebo or oral antioxidative treatment (Quatral(R)) once daily for 16 weeks. Study parameters were increase of lag phase (DeltaLAG) and the ratio of lag phase during treatment period versus baseline (relative oxidation resistance, ROR), measured by Cu2+-induced oxidation of isolated LDL. Hp phenotypes were determined by starch gel electrophoresis. A significant and persistent increase of DeltaLAG (P < 0.05) and ROR (P < 0.01) were observed after 16 weeks of active treatment versus placebo. Interindividual differences in both parameters were significantly associated with the Hp polymorphism: in the active treatment group, DeltaLAG and ROR were significantly higher in Hp 1-1 subjects (P < 0.01) compared to Hp 2-1 and 2-2. Our data demonstrate that Hp phenotype is one of the modulating factors determining the increased resistance to Cu2+-induced oxidation of LDL during antioxidative treatment.