PT  - JOURNAL ARTICLE
AU  - Margaret M. Parker
AU  - Simina Ticau
AU  - James Butler
AU  - David Erbe
AU  - Madeline Merkel
AU  - Emre Aldinc
AU  - Gregory Hinkle
AU  - Paul Nioi
TI  - Transthyretin-stabilizing mutation T119M is not associated with protection against vascular disease or death in the UK Biobank
AID  - 10.1101/771626
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 771626
4099  - http://biorxiv.org/content/early/2019/09/21/771626.short
4100  - http://biorxiv.org/content/early/2019/09/21/771626.full
AB  - Background Destabilized transthyretin (TTR) can result in the progressive, fatal disease transthyretin-mediated (ATTR) amyloidosis. A stabilizing TTR mutation, T119M, is the basis for a therapeutic strategy to reduce destabilized TTR. Recently, T119M was associated with extended lifespan and lower risk of cerebrovascular disease in a Danish cohort. We aimed to determine whether this finding could be replicated in the UK Biobank.Methods TTR T119M carriers were identified in the UK Biobank, a large prospective cohort of ∼500,000 individuals. Association between T119M genotype and inpatient diagnosis of vascular disease, cardiovascular disease, cerebrovascular disease, and mortality was analyzed.Results Frequency of T119M within the white UK Biobank population (n=337,148) was 0.4%. Logistic regression comparing T119M carriers to non-carriers found no association between T119M and vascular disease (odds ratio [OR]=1.08; p=.27), cardiovascular disease (OR=1.08; p=.31), cerebrovascular disease (OR=1.1; p=.42), or death (OR=1.2; p=.06). Cox proportional hazards regression showed similar results (hazard ratio>1, p>.05). Age at death and vascular disease diagnosis were similar between T119M carriers and non-carriers (p=.12 and p=.38, respectively).Conclusions There was no association between the TTR T119M genotype and risk of vascular disease or death in a large prospective cohort study, indicating that TTR tetramer stabilization through T119M is not protective in this setting.