Hamidi Asl K, Liepnieks J J, Nakamura M, Parker F, Benson M D
Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Biochem Biophys Res Commun. 1999 Apr 13;257(2):584-8. doi: 10.1006/bbrc.1999.0518.
An American kindred was found to have hereditary amyloidosis with cutaneous and cardiac involvement. Characterization of fibrils isolated from skin identified the amyloid protein as the N-terminal 90 to 100 residues of apolipoprotein A-1. Sequence of the apolipoprotein A-1 gene was normal except for a G/C transversion at position 1638 which predicts an Arg to Pro substitution at residue 173. This mutation, unlike previously described amyloidogenic mutations is not in the N-terminal fragment which is incorporated into the fibril. The mutation is at the same residue as in apolipoprotein A-1 Milano (Arg173Cys) which does not result in amyloid formation. Decreased plasma HDL cholesterol levels in carriers of the Arg173Pro mutation suggest an increased rate of catabolism as has been shown for the amyloidogenic Gly26Arg mutation. This suggests that altered metabolism caused by the mutation may be a significant factor in apolipoprotein A-1 fibrillogenesis.
发现一个美国家族患有伴有皮肤和心脏受累的遗传性淀粉样变性。从皮肤中分离出的原纤维的特征表明，淀粉样蛋白是载脂蛋白A-1的N端90至100个残基。载脂蛋白A-1基因的序列正常，只是在第1638位发生了G/C颠换，预测在第173位残基处由精氨酸替换为脯氨酸。与先前描述的淀粉样变性突变不同，该突变不在掺入原纤维的N端片段中。该突变与载脂蛋白A-1米兰型（Arg173Cys）的突变位于相同残基处，后者不会导致淀粉样蛋白形成。Arg173Pro突变携带者的血浆高密度脂蛋白胆固醇水平降低，表明分解代谢率增加，正如淀粉样变性Gly26Arg突变所显示的那样。这表明该突变引起的代谢改变可能是载脂蛋白A-1纤维形成的一个重要因素。
