Transthyretin-stabilising mutation T119M is not associated with protection against vascular disease or death in the UK Biobank

• Published in: Amyloid Vol. 27; no. 3; pp. 184 - 190
• Main Authors: Parker, Margaret M., Ticau, Simina, Butler, James, Erbe, David, Merkel, Madeline, Aldinc, Emre, Hinkle, Gregory, Nioi, Paul
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02-07-2020
• Subjects: Genetic association analysis; hereditary transthyretin-mediated amyloidosis; survival analysis; T119M; UK Biobank; vascular disease; hereditary transthyretin-mediated amyloidosis; survival analysis; vascular disease; UK Biobank; T119M; Genetic association analysis
• ISSN: 1350-6129; 1744-2818
• DOI: 10.1080/13506129.2020.1758658

Background: Destabilised transthyretin (TTR) can result in the progressive, fatal disease transthyretin-mediated (ATTR) amyloidosis. A stabilising TTR mutation, T119M, is the basis for a therapeutic strategy to reduce destabilised 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 analysed.
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 stabilisation through T119M is not protective in this setting.