Investigation into thiol conjugation of transthyretin in hereditary transthyretin amyloidosis.
BACKGROUND
For all forms of amyloidosis, the amyloid-generating mechanism is unknown. Familial amyloidotic polyneuropathy type I is caused by a variant transthyretin (TTR Met-30). As electrospray ionization mass spectrometry (ESI-MS) discloses both thiol-conjugated and -unconjugated forms of wild-type and variant TTR, we wanted to investigate the relationship between TTR conjugation and clinically overt amyloid disease.


METHODS
Plasma from 35 individuals (12 symptomatic TTR Met-30 carriers, nine asymptomatic and 14 healthy control subjects) were analysed using ESI-MS.


RESULTS
The total TTR concentration was significantly lower in symptomatic TTR Met-30 carriers than in control subjects. An increased percentage of conjugated TTR Met-30 was found in symptomatic carriers compared with asymptomatic, whereas the percentage conjugated wild-type TTR was similar for control subjects, asymptomatic and symptomatic TTR Met-30 carriers.


CONCLUSIONS
The finding of a decreased ratio of unconjugated to conjugated TTR Met-30 in plasma samples from symptomatic TTR Met-30 carriers indicates that thiol conjugation of TTR could be involved in amyloid formation.
Department of Medicine, Umeå University Hospital, Sweden. ole.suhr@medicin.umu.se
O B
OB
Suhr
Y
Y
Ando
P I
PI
Ohlsson
A
A
Olofsson
K
K
Andersson
E
E
Lundgren
M
M
Ando
G
G
Holmgren
D000328:Adult; D000368:Aged; D017772:Amyloid Neuropathies / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D008970:Molecular Weight; D017354:Point Mutation; D011228:Prealbumin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*
D011228:Prealbumin; D013438:Sulfhydryl Compounds