| Title: | Transthyretin-stabilising mutation T119M is not associated with protection against vascular disease or death in the UK Biobank |
| Journal: | Amyloid |
| Published: | 19 May 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32425064/ |
| DOI: | https://doi.org/10.1080/13506129.2020.1758658 |
| URL: | https://www.tandfonline.com/doi/pdf/10.1080/13506129.2020.1758658?needAccess=true |
| Citations: | 3 (2 in last 2 years) as of 8 Aug 2024 |
Publication 5922
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Abstract
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.</p>
13 Keywords
- Amyloid Neuropathies, Familial
- Biological Specimen Banks
- Cerebrovascular Disorders
- Death
- Denmark
- Genetic Association Studies
- Genotype
- Heterozygote
- Humans
- Mutation
- Prealbumin
- Risk Factors
- United Kingdom
8 Authors
- Margaret M. Parker
- Simina Ticau
- James Butler
- David Erbe
- Madeline Merkel
- Emre Aldinc
- Gregory Hinkle
- Paul Nioi
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