Increased circulating malondialdehyde-modified LDL in the patients with familial combined hyperlipidemia and its relation with the hepatic lipase activity

Familial combined hyperlipidemia (FCHL) is characterized by elevated levels of serum total cholesterol (TC), triglyceride (TG), or both. The increased incidence of coronary artery diseases (CAD) in the patients with FCHL is believed to be caused by circulating atherogenic lipoproteins associated with the complex phenotype. Recent establishment of sensitive detection system for malondialdehyde-modified (MDA)-LDL, which is one of oxidized lipoproteins, showed its increased circulating level in the patients with CAD. In order to know the atherogenic lipoproteins resulted from the dyslipidemia observed in FCHL, we measured the serum MDA-LDL level in the patients. The circulating MDA-LDL level and the ratio of MDA-LDL and LDL-C in FCHL were significantly higher (P<0.05) than those in control, which are adjusted about the age, serum TC, LDL-C and HDL-C levels, respectively. Furthermore, the circulating MDA-LDL level and the ratio of MDA-LDL and LDL-C were negatively correlated (R=-0.635, P<0.01 and R=-0.702, P<0.01, respectively) with hepatic lipase (HL) activity in FCHL. The serum MDA-LDL level and the ratio of MDA-LDL and LDL-C were in the subjects with T/T genotypes in the HL C-514T polymorphism were significantly increased compared to those with C/C genotype, respectively. The subjects with T/T genotype showed the activities to 65 and 79% of those in the subjects with C/C genotype in male and female, respectively. The intima-media thickness (IMT) of carotid artery was significantly higher (P<0.05) in the subjects with T/T genotype than those with C/C genotype in male. These findings indicate that the circulating MDA-LDL level is possibly contributing the atherogenic process in FCHL, and the common HL polymorphism might be a determinant of the serum level of oxidized LDL in the patients with FCHL.