Oxidized low-density lipoprotein, iron stores, and haptoglobin polymorphism

Background: In vitro experimental studies demonstrated that iron promotes free radical-induced low-density lipoprotein (LDL) oxidation. Objective: To test the hypothesis that circulating oxidized LDL (oxLDL) levels might be associated with body iron stores (serum ferritin) and iron-related genetic markers (hemochromatosis gene C282Y mutation, haptoglobin polymorphism). Methods: We investigated 381 (176 males, 205 females, age 45 6 years) healthy Caucasians. Serum oxLDL, assayed by a mAb-4E6-based enzyme-linked immunosorbent assay (ELISA), was expressed as oxLDL/LDL ratio to adjust for serum LDL-cholesterol concentration. Hemochromatosis gene C282Y mutation analysis was performed by a Taqman(R)-based polymerase chain reaction (PCR) assay. Haptoglobin (Hp) phenotypes (Hp 1-1, Hp 2-1, Hp 2-2) were determined by starch gel electrophoresis. Results: In stepwise multivariate regression analysis, gender (P < 0.0001), current smoking (P < 0.0001), HDL-cholesterol (P = 0.0001), ferritin (P = 0.0051), body mass index (BMI) (P = 0.0063), and Hp phenotype (P = 0.0331) independently predicted oxLDL/LDL ratio in the total group. In men, smoking(P < 0.0001), ferritin (P = 0.0052), Hp phenotype (P = 0.0063),and HDL-cholesterol(P = 0.0127) were independent determinants of oxLDL/LDL ratio. In women, only body mass index (P < 0.0001),HDL-cholesterol (P = 0.0005), and smoking (P = 0.0025) were significantly associated with oxLDL/LDL ratio. The C282Y mutation (wild-type versus C282Y heterozygotes) was not associated with oxLDL/LDL ratio in both sexes. Conclusion: Serum ferritin concentration and Hp polymorphism are independently associated with circulating oxLDL levels in males. (C) 2004 Elsevier Ireland Ltd. All rights reserved.