DECREASED AFFINITY OF APOLIPOPROTEIN ALL TO HIGH-DENSITY-LIPOPROTEIN IN PATIENTS WITH TRANSTHYRETIN-RELATED AMYLOIDOSIS (MET30, GLN89, PRO36, AND THR34)

We previously reported that patients with familial amyloidotic polyneu ropathy (FAP) (Met30) showed low plasma apolipoprotein AII (apoAII) le vels and apolipoprotein AII/AI (apoAII/AI) ratio as the progression of the disease while plasma levels of apoAI, B, CII, CIII, and E were al l within normal ranges. In the present study, we investigated these ap olipoproteins contained in high density lipoprotein (HDL) extracted fr om plasma of FAP patients with various types of mutations (Gln89, Pro3 6, and Thr34) by ultracentrifugation in addition to FAP (Met30), and t he levels of apoAII gene expression in the liver from patients with FA P (Met30). Plasma apoAII levels and the apoAII/AI ratio in extracted H DL in all the FAP types examined decreased compared with those in norm al control subjects. Levels of apoAII mRNA expression in the Liver of FAP (Met30) patients did not show significant changes compared with th ose in control subjects. These results suggest that decreased affinity of apoAII to HDL could not be compensated by overproduction of apoAII in the liver of the FAP patients and as a result of this phenomenon, plasma apoAII levels might decrease as the progression of FAP. (C) 199 6 Academic Press, inc.