Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy
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Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy. / Hornstrup, Louise S; Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Tybjærg-Hansen, Anne.
I: Arteriosclerosis, Thrombosis, and Vascular Biology, Bind 33, Nr. 6, 06.2013, s. 1441-7.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy
AU - Hornstrup, Louise S
AU - Frikke-Schmidt, Ruth
AU - Nordestgaard, Børge G
AU - Tybjærg-Hansen, Anne
PY - 2013/6
Y1 - 2013/6
N2 - Transthyretin can cause amyloidosis attributable to destabilization of transthyretin tetramers in plasma. We tested the hypothesis that genetic stabilization of transthyretin associates with reduced risk of vascular disease and increased life expectancy. APPROACH AND RESULTS: We included 68 602 participants from 2 prospective studies of the general population. We genotyped for 2 stabilizing genetic variants in the transthyretin gene (TTR), R104H and T119M, and determined the association of genotypes with plasma levels of transthyretin, measures of thyroid function, risk of vascular disease, and life expectancy. During a mean follow-up of 32 years, 10 636 participants developed vascular disease. We identified 321 heterozygotes for T119M (frequency, 0.47%); R104H was not detected. First, mean plasma transthyretin and thyroxine levels were increased by 17% (26 µg/mL) and 20% (19 nmol/L), respectively, in heterozygotes versus noncarriers (P=0.007 and P
AB - Transthyretin can cause amyloidosis attributable to destabilization of transthyretin tetramers in plasma. We tested the hypothesis that genetic stabilization of transthyretin associates with reduced risk of vascular disease and increased life expectancy. APPROACH AND RESULTS: We included 68 602 participants from 2 prospective studies of the general population. We genotyped for 2 stabilizing genetic variants in the transthyretin gene (TTR), R104H and T119M, and determined the association of genotypes with plasma levels of transthyretin, measures of thyroid function, risk of vascular disease, and life expectancy. During a mean follow-up of 32 years, 10 636 participants developed vascular disease. We identified 321 heterozygotes for T119M (frequency, 0.47%); R104H was not detected. First, mean plasma transthyretin and thyroxine levels were increased by 17% (26 µg/mL) and 20% (19 nmol/L), respectively, in heterozygotes versus noncarriers (P=0.007 and P
U2 - 10.1161/ATVBAHA.113.301273
DO - 10.1161/ATVBAHA.113.301273
M3 - Journal article
C2 - 23580146
VL - 33
SP - 1441
EP - 1447
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 6
ER -
ID: 48539695