التفاصيل البيبلوغرافية
| العنوان: |
The V122I Variant in Hereditary Transthyretin-Mediated Amyloidosis is Significantly Associated with Polyneuropathy. |
| المؤلفون: |
Parker, Margaret M., Damrauer, Scott M., Tcheandjieu, Catherine, Erbe, David, Aldinc, Emre, Hawkins, Philip N., Gillmore, Julian, Hull, Leland E., Lynch, Julie A., Joseph, Jacob, Ticau, Simina, Flynn-Carroll, Alexander O., Deaton, Aimee M., Ward, Lucas D., Assimes, Themistocles L., Tsao, Philip S., Chang, Kyong-Mi, Rader, Daniel J., Fitzgerald, Kevin, Vaishnaw, Akshay K. |
| المصدر: |
Journal of Cardiac Failure; 2020 Supplement, Vol. 26 Issue 10, pS96-S96, 1p |
| مستخلص: |
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressively debilitating disease caused by mutations in the transthyretin (TTR) gene. The V122I variant, a common pathogenic TTR mutation found primarily in individuals of West African descent, is frequently associated with cardiomyopathy. Other hATTR amyloidosis manifestations have been reported in some carriers of the V122I variant, yet the association remains unclear. The V122I variant may be associated with common hATTR amyloidosis manifestations beyond cardiomyopathy. The association between the V122I variant and ICD10 diagnosis codes was assessed in the UK Biobank (UKBB) black subpopulation (n = 6,062) with replication of significant associations in the Penn Medicine Biobank (PMBB) (n = 5,737) and the VA Million Veteran Program (MVP) (n = 82,382). The cumulative incidence of common hATTR amyloidosis manifestations (polyneuropathy, carpal tunnel syndrome, cardiomyopathy, and heart failure) was estimated by V122I genotype in the UKBB using Cox regression controlling for age, sex and genetic ancestry. Of the 6,062 participants in the UKBB, 243 were V122I carriers. Common hATTR amyloidosis manifestations in the UKBB were significantly enriched in V122I carriers compared with non-carriers (HR = 2.8, P = 2.6 × 10−5). Phenome-wide analysis identified a significant association between the V122I genotype and polyneuropathy diagnosis (OR = 6.4, P = 4.24 × 10−5) in the UKBB, which was replicated in both the PMBB (OR = 1.6, P = 6.0 × 10−3) and the MVP (OR = 1.48, P = 1.8 × 10−4). Prevalence of a polyneuropathy diagnosis among V122I carriers was 2.1%, 9.0%, and 4.8% in the UKBB, PMBB, and MVP, respectively. By age 75, 37.4% of V122I carriers in the UKBB had a diagnosis of at least one of the common manifestations, including 7.9% with polyneuropathy. Yet, only 0.8% of carriers had a formal diagnosis of hATTR amyloidosis. The V122I variant, historically associated with cardiomyopathy, is also significantly associated with an increased risk of polyneuropathy. [ABSTRACT FROM AUTHOR] |
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