Tangier disease homozygotes had a markedly reduced mean plasma-residence time for HDL apolipoproteins compared to normal subjects (0.52 vs 5.21 days) due to rapid and altered catabolism.
Observational (n=15)
What is the metabolic defect responsible for the deficiency of high-density lipoprotein apolipoproteins in Tangier disease?
The deficiency of HDL apolipoproteins in Tangier disease is primarily driven by rapid and altered catabolism rather than decreased synthesis.
Absolute Event Rate: 0.52% vs 5.21%
To define the metabolic defect in Tangier disease, we studied the kinetics of 125I-high-density lipoprotein apolipoproteins (apolipoproteins A-I and A-II) in 11 normal subjects, two obligate heterozygotes, and two homozygotes. Mean synthesis of apolipoproteins A-1 and A-11 was 8.24 mg per kilogram per day in the normal group, 7.94 in heterozygotes and 3.66 in homozygotes. The mean plasma-residence time for both apolipoproteins was 5.21 days in the normal subjects, 3.41 days in heterozygotes, and 0.52 days in homozygotes. In normal subjects and heterozygotes the apolipoproteins were catabolized at similar rates, whereas in homozygotes apolipoprotein A-I was catabolized at a much greater fractional rate than apolipoprotein A-II. These findings indicate that the deficiency of these apolipoproteins in Tangier disease is largely due to rapid and altered catabolism.
Schaefer et al. (Thu,) conducted a observational in Tangier disease (n=15). Tangier disease (homozygosity) vs. Normal subjects was evaluated on Mean plasma-residence time for apolipoproteins A-I and A-II (days). Tangier disease homozygotes had a markedly reduced mean plasma-residence time for HDL apolipoproteins compared to normal subjects (0.52 vs 5.21 days) due to rapid and altered catabolism.