Waits R P, Yamada T, Uemichi T, Benson M D
Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis, USA.
Clin Chem. 1995 Sep;41(9):1288-91.
Retinol-binding protein (RBP), the principal carrier for vitamin A, is known to form a complex with transthyretin (TTR) for transport in plasma. Individuals from a kindred with the amino acid substitution of serine for isoleucine at position 84 (Ser84) of the TTR molecule show substantial reduction in plasma concentrations of RBP. In the present study, we measured plasma RBP in individuals from several kindreds, demonstrating 17 different point mutations within the TTR gene. In each case, these mutations caused single amino acid substitutions at various positions throughout the TTR molecule. Of all the individuals examined, only those with mutations causing amino acid substitutions at position 84 of the TTR molecule (Ser84 and Asn84) demonstrated substantial decreases in plasma concentrations of RBP. These results suggest that the isoleucine at position 84 on the TTR molecule may be critically involved in mediating RBP binding. Further, these findings demonstrate the importance of considering TTR gene mutations when clinically evaluating patients with low RBP.
视黄醇结合蛋白（RBP）是维生素A的主要载体，已知它会与甲状腺素转运蛋白（TTR）形成复合物以便在血浆中运输。来自一个家系的个体，其TTR分子第84位氨基酸异亮氨酸被丝氨酸取代（Ser84），血浆中RBP浓度大幅降低。在本研究中，我们检测了来自几个家系个体的血浆RBP，发现TTR基因内有17种不同的点突变。在每种情况下，这些突变导致TTR分子各处不同位置的单个氨基酸替换。在所有检测的个体中，只有那些TTR分子第84位氨基酸发生替换突变的个体（Ser84和Asn84）血浆RBP浓度大幅降低。这些结果表明，TTR分子第84位的异亮氨酸可能在介导RBP结合中起关键作用。此外，这些发现证明了在临床评估RBP水平低的患者时考虑TTR基因突变的重要性。
