Several reports have suggested that HDL has anti-oxidative actions. We investigated the relationship between HDL-cholesterol (HDL-C) and malondialdehyde-modified LDL (MDA-LDL) concentrations using enzyme linked immunosolvent assay. We divided our study subjects into four groups on the basis of concentrations of triglyceride (TG) and HDL-C by the following lipid profiles: serum TG < or = 1.69 mmol/L and HDL-C > or = 1.16 mmol/L (control group, n = 26); TG >1.69 and HDL-C < or = 1.16 (high TG group, n = 22); TG >1.69 and HDL-C < or = 0.91 (high TG & low HDL group, n = 67); TG < or = 1.69 and HDL-C < or = 0.91 (low HDL group, n = 21). MDA-LDL concentrations, MDA-LDL/apolipoprotein B (apo B) ratio, and LDL size were different between subjects in high TG & low HDL and control groups. MDA-LDL concentrations in both high TG and low HDL groups did not differ significantly from those in the control. However, MDA-LDL/apo B ratio in low HDL group was significantly higher than that in the control (P < 0.05). The MDA-LDL/apo B ratio reflects the extent of MDA modification of apo B in LDL. Therefore, our data suggest that as HDL-C concentrations fall, the extent of MDA modification per one LDL particle increases. Moreover, accompanied by high TG concentration, LDL size in subjects with lower HDL-C concentrations became smaller.

A high serum triglyceride (TG) concentration is associated with an increased serum concentration of small, dense low-density lipoprotein (LDL). To further characterize the hypertriglyceridemic condition, we examined sera from 240 subjects for small, dense LDL using non-denaturing polyacrylamide gradient gel electrophoresis. We focused on determining the frequency of the pattern B, which is characterized by a higher proportion of small, dense LDL, among hypertriglyceridemic individuals. The subjects were divided into four groups: a control group (TG < or = 1.65 mmol/l, high-density lipoprotein cholesterol (HDL-C) > or =1.17 mmol/l; n = 71), a high TG group (TG > 1.65 mmol/l, HDL-C > or = 1.17 mmol/l; n = 36), a group with high TG and low HDL-C (TG > 1.65 mmol/l, HDL-C < or = 0.91 mmol/l; n = 106), and a low HDL-C group (TG < or = 1.65 mmol/l, HDL-C < or = 0.91 mmol/l; n = 27). We found that pattern B occurs at a high frequency mainly in individuals with high TG and low HDL-C levels. We also observed an increased percentage of LDL within the 20.0 nm to 25.5 nm particle diameter range in this group. Analysis of the lipoprotein lipase gene in this group showed that some mutations seem to be associated with small, dense LDL, resulting in LDL pattern B.

To investigate the relationship between the lipoprotein lipase Ser447Ter (S447X) mutation, lipid profiles and risk of atherosclerotic disease, we studied two groups of Japanese subjects. These groups consisted of a dyslipidemic group (triglyceride (TG) > 1.69 mmol/l and high-density lipoprotein-cholesterol (HDL-C) < or = 0.91 mmol/l; n = 106) and a control group (TG < or = 1.69 mmol/l and HDL-C > or = 1.16 mmol/l; n = 106). All subjects in the control group were confirmed to the pattern A phenotype (normal low-density lipoprotein (LDL) pattern), and 21 individuals in this group were heterozygous for the S447X mutation, but not homozygous. In the patient group, pattern A was shown by 44 of 106 patients. The rest were of the pattern B phenotype, which is associated with an increased risk of coronary heart disease. Homozygosity was concentrated in the patient group (p < 0.05) and in those with the pattern B phenotype (p < 0.05). In contrast, heterozygosity between both groups was not statistically significant. In conclusion, heterozygous and homozygous status with respect to the LPL S447X mutation appears to have different meanings with respect to biochemical and clinical phenotypes of atherosclerosis.