Proportion between wild-type and mutant protein in truncated compared to full-length ATTR: an analysis on transplanted transthyretin T60A amyloidosis patients
2009 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 379, no 4, 846-850 p.Article in journal (Refereed) Published
Familial ATTR amyloidosis is caused by point mutations in the transthyretin gene. The clinical manifestations are highly varied but polyneuropathy and/or cardiomyopathy are generally the main symptoms. The amyloid fibrils can either be composed of only intact ATTR molecules or intact together with fragmented ATTR species. As plasma TTR is almost exclusively synthesized in the liver, liver transplantation is performed in order to eliminate the mutant plasma TTR. The procedure has shown best results among patients with the V30M mutation, while a rapid continued cardiac deposition of wild-type (wt) TTR has been seen for many other mutations. In this paper we investigated the proportion of wtATTR in two TTRT60A patients that underwent liver transplantation; one patient died 3 weeks after surgery, the other patient survived for 12 months. As the role of fragmented TTR species in the pathogenesis is far from understood, we investigated the proportion of wt in these species separately to the full-length molecules, which has not been done before in transplanted patients. The results show a higher proportion of wtTTR in the 12-months-surviving patient than the 3-weeks-surviving patient, but interestingly this difference in wt proportion is mainly seen among the full-length, and not the fragmented, molecules.
Place, publisher, year, edition, pages
2009. Vol. 379, no 4, 846-850 p.
Amyloid, Transthyretin, Familial amyloidotic polyneuropathy, ATTRT60A, Liver transplantation, Fibril, Cardiomyopathy, Wild-type
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-103620DOI: 10.1016/j.bbrc.2008.12.095ISI: 000263336700009PubMedID: 19118530OAI: oai:DiVA.org:uu-103620DiVA: diva2:218579