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-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.


CONCLUSIONS
Serum ferritin concentration and Hp polymorphism are independently associated with circulating oxLDL levels in males.
Department of Clinical Chemistry and Haematology, AZ St-Jan AV Hospital, Ruddershove 10, B-8000 Bruges, Belgium.
Annelies
A
Brouwers
Michel
M
Langlois
Joris
J
Delanghe
Johan
J
Billiet
Marc
M
De Buyzere
Raf
R
Vercaemst
Ernst
E
Rietzschel
Dirk
D
Bernard
Victor
V
Blaton
D000328:Adult; D005260:Female; D005293:Ferritins / Q000097:blood*; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D012044:Regression Analysis
C103673:HFE protein, human; D006242:Haptoglobins; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; C099252:oxidized low density lipoprotein; D005293:Ferritins; D007501:Iron