Sources of Funding: This work was supported by the Danish Medical Research Council (grant no. 09-065553), the Lundbeck Foundation, the Research Fund at Rigshospitalet, Copenhagen University Hospital, Chief Physician Johan Boserup and Lise Boserups fund, Aase and Ejnar Danielsens grant, Ingeborg and Leo Dannins grant, Henry Hansen and Wifes grant, and a grant from the Order of Odd Fellows; all from Copenhagen, Denmark.

Dietary factors such as resveratrol (active component in red grapes/red wine), curcumin (major bioactive polyphenol of turmeric), andpopulation. 

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Iodinated transthyretin derivatives are candidate drugs for transthyretin amyloidosis, showing improved stability compared with transthyretin. Thyroxine binding stabilizes transthyretin through 4 iodine substituents, and there are additional binding sites for thyroxine left unbound on transthyretin. Hence, total plasma iodine levels may correlate with transthyretin levels and may be higher in individuals with higher transthyretin levels, such as in T119M heterozygotes because transthyretin binds more thyroxine and therefore more iodine.

Further limitations to our study include that we only examined whites and therefore our findings may not translate to populations of other ethnicities. However, because T119M is present in both whites of European ancestry and in blacks of African American ancestry, the effect of T119M in humans is probably not ethnicity-specific. Nevertheless, large studies of other ethnic groups are needed to address this issue. Finally, R104H, a genetic variant previously identified in Asians, was not detected in our study but may have similar protective effects as T119M in Asian populations.

In the present study, we show that genetic stabilization of transthyretin attributable to heterozygosity for T119M protects against cerebrovascular disease. Thus, our data could suggest that T119M protects against amyloid deposition in the brain. 

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